Clinical Genetics 1979: 15: 317-326
Chromosome 8 abnormalities as components of neoplastic and hematologic disorders VINCENT M. RICCARDI AND JUDY FORGAS'ON
Kleberg Genetics Center, Baylor College of Medicine, Texas Medical Center, Houston, Texas, U. S. A. Publications involving patients with any abnormality of chromosome 8 have been reviewed in detail. For the time period involved, a total of 277 cases were found, including 74 instances of congenital aneuploidy, 130 instances of acquired aneuploidy, 38 instances of congenital rearrangements, and 35 instances of acquired rearrangements. A total of 170 cases of neoplastic and hematologic disorders were included; three were associated with congenital aneuploidy, two with congenital rearrangements, and the remaining 165 with acquired aberrations. The specific disorders ranged from sideroblastic anemia through chronic and acute leukemia to solid tumors. There appears to be a definite, though nonspecific correlation between congenital or acquired chromosome 8 abnormalities and the development of certain types of neoplastic growth. Received 30 May, revised 2 November, accepted for publication 17 November 1978 K e y words: Cancer; chromosome 8; leukemia; neoplasia.
Increasingly, both benign and malignant neoplasia are being considered in genetic terms. Chromosomes, as units of organization of the cell's genetic material, have become especially important in our efforts t o understand the etiology, pathogenesis, and natural history of various types of neoplasia, including cancer (Atkin 1971, Nowell 1976, Rowley 1977). I n some instances chromosome aberrations clearly seem to cause tumors (e.g., chromosome 13 long arm deletions and retinoblastomas (Knudson et al. 1976)), while in most other instances it is not clear whether associated chromosome aberrations cause the neoplasm, a r e conssquences of the malignant transformation process(es), or are merely
incidental accompaniments. T h e best known association of cancer with chromosome derangement is that of chronic myelogenous leukemia (CML) and the Philadelphia chromosome (Nowell & Hungerford 1960, Mitelman 1974). Among the other recognized associations, perhaps the potentially most informative involve chromosome 8 because several types of abnormalities have been noted in a variety of malignancies. Starting from our previous interests in the consequences of congenital trisomy 8 and terminal 8q triplications (Riccardi 1977), we have reviewed published data dealing with known aberrations of chromosome 8 and their associations with neoplasia.
0009-9163/79/040317-10 $02.50/0 0 1979 Munksgaard, Copenhagen
31 8
RlCCARDl AND FORGASON
Materials and Methods
Individual case reports and reviews through July 1977 were ascertained by utilizing standard medical and biological reference indices, as well as a computerized literature search. The index topics were “human chromosome 8”, “chromosomes and malignancy”, and “chromosomes and hematologic disorders”. All articles that included at least one case with a chromosome 8 aberration were abstracted. In some instances an author of a paper was personally contacted to clarify or update the published data. Only those studies which utilized chromosome banding techniques were included. Additional articles dealing with other chromosomal anomalies in neoplasia were reviewed t o provide a context for appreciating the relative role of chromosome 8 in neoplastic disorders (Atkin 1971, Atkin & Pickthall 1977, Giovanella et al. 1976, Gunz et al. 1973, Hart et al. 1971, Levan & Mitelman 1975, Rowley 1975b), but no effort was made to determine the proportion of chromosome 8 aberrations either among all neoplasias or among chromosomally abnormal neoplasias. Methodologic problems were of three types: 1. Inclusion of the same patient or groups of patients in sequential reports and reviews, without intrinsic mechanisms for clarification; 2 . Failure of many authors to associate specific cytogenetic findings with specific patients; and 3. Many instances where a chromosome 8 abnormality was only one of several cytogenetic aberrations. The first two problems were handled by careful cross-checking and by inquiries of selected authors. The third problem was handled by our decision to include the case as an instance of chromosome 8 abnormalities whether or not other chromosomes
were involved. In those instances of congenital chromosome 8 aberrations where multiple family members were involved, only one case per family was tallied. The term “acquired chromosome abnormality” indicates that the chromosome abnormality was not congenital and that it evolved within the neoplastic cell population (with one exception (Riccardi et al. 1978a)). Although purely inferential, this definition is supported by investigations on the “premalignant” state (Linman & Bagby 1976, Panani et al. 1977), and certain heritable disorders predisposing to leukemia (Hook et al. 1975). Results
As indicated in Table 1 , we ascertained 277 cases with either a missing, extra, deleted, translocated, or otherwise abnormal chromosome 8. In 112 cases the chromosome abnormality was congenital, involving either trisomy (almost always mosaic) or rearrangements, balanced or unbalanced. As seen in Table 2, three patients with congenital trisomy 8 were found to have a malignancy: acute non-lymphocytic leukemia (Gafter et al. 1976), Wilms tumor (Niss & Passarge 1976) and prostatic rhahdomyosarcoma (Danks & Sillence 1977). One patient with a translocation had a Wilms tumor (Ladda et al. 1974), although the complex chromosome rearrangement actually involves a net loss of a portion of I l p (Francke, U. & Riccardi, V. M., unpublished data) and thus will not be included here. Two congenital translocation patients had distinctive anemias. Most of the patients with congenital chromosome 8 defects were young children, and many had died as youngsters, perhaps before a neoplastic diathesis could he manifest. The remaining 165 cases (Table 1) had acquired chromosome 8 abnormalities, recognized as part of evaluations for hemato-
CHROMOSOME 8 AND NEOPLASIA Table 1 Types of chromosome 8 aberrations and numbers ascertained No. ascertained Acquired aberrations Aneuploidy Rearrangements
130’ 352
Congenital aberrations Aneuploidy Rearrangements
743 384
Total aberrations
165
112
277
Rowley (1977, 1975b), Riccardi et al. (1978a), Panani et al. (19771, Yamada & Furusawa (1976), Lindgren & Rowley (1977). Jonasson et al. (1974), Lawler et al. (1975a, b), Mitelman et al. (1976), Oshimura et al. (1976), Philip (1975), Philip et al. (1977), Sakurai & Sandberg (1976), Rowley & Sandberg (1977). de la Chapelle et al. (1976), Engel et al. (1975, 1977), Gahrton et at. (1974). Hayata et al. (1975). Hsu et al. (1974). Mitelman et al. (1975), Prigogina & Fleischman (1975), Rowley (1973a), Mitelrnan et al. (1974), Baker (1968), Patil et al. (1978), Sonta et al. (1977), Mark (1973a, b), Mark et al. (1972a, b), Ford 8 Pittman (1974), Ford et al. (1975), Tiepolo 8 Zuffardi (19731, Rowley (1973~).Weinfeld et al. (1977), Mitelman & Levan (1976). Bitran et al. (1977). Helistrom et al. (1971). Yamada & Furusawa (1976), Lindgren 8. Rowley (1977). Lawler et al. (1975a), Oshimura et al. (1976), Sakurai & Sandberg (1976), Engel et al. (1975), Rowley (1973b, 1974), Sakurai et al. (1974), McCaw et al. (1977), Zech et al. (1976), Berger et al. (1974), Berger & Lacour (1974). 3 Riccardi (1977), Bernsen et al. (1977). Blair (1976), Gafter et al. (1976), Gellis et al. (1975), Koszyolanyi et al. (19761, Niss & Passarge (1976). DeGrouchy et al. (1974), Kondo (1976). Danks & Sillence (1977). Riccardi (1977). Kirnberling et al. (1975), Biederrnan Bowen (1977), Fried et al. (1977), Herva 8 de la Chapelle (1976), Kawana e t al. (1976). Bresson et al. (1977), Sanchez 8 Yunis (1974), Fryns et al. (1974), Fujimoto et al. (1975), Ladda et al. (1974), Orye & Craen (1976). Reiss et al. (1977), Rethore et al. (1977), Rodewald et al. (1977), Rosenthal et al. (1973), Schinzel (1977). Taillemete et ai. (1975). Weleber et al. (1976), Wurster-Hill & Hoefnagel (1974), Yanagisawa (1973), Guanti et al. (1976), Lin er al. (1975), Niebuhr (1973).
logic or neoplastic disorders. Aneuploidy was noted 130 times, including trisomy 8 in 105 instances, while rearrangements accounted for 35 cases. As summarized in Table 2 , among the trisomy 8 cases 6 4 % (67 out of 105) were
319
seen in association with AML (Riccardi et al. 1978a, Yamada & Furusawa 1976, Lindgren & Rowley 1977, Jonasson et al. 1974, Lawler et al. 1975a, Mitelman et al. 1976, Oshimura et al. 1976, Philip 1975, Philip et al. 1977, Sakurai & Sandberg 1976, Rowley & Sandberg 1977) and the blastic phase of CML (Rowley 1977, de la Chapelle et al. 1976, Engel et al. 1975, 1977, Gahrton et al. 1974, Hayata et al. 1975, Hsu et al. 1974, Lawler et al. 1975b, Mitelman et al. 1975, Prigogina & Fleischman 1975, Rowley 1973a, 1975a). and 1070 (11 out of 105) were seen in solid tumor cells, most notably colorectal cancers (Kakati et al. 1976, Mitelman et al. 1974, Baker 1968, Patil et al. 1978, Sonta et al. 1977). Monosomy 8 was associated with meningiomas (17 times) (Mark 1973a, b, Mark et al. 1972a, b) but was also noted five times in AML and CML (Hayata et al. 1975, Ford & Pittman 1974, Ford et al. 1975). In the “other aneuploidy” category, two ovarian adenocarcinomas (from two separate patients) showed mosaic nullisomy 8 (Tiepolo & Zuffardi 1973). The most distinctive acquired rearrangements were the 8;21 translocation characteristic of AML (Yamada & Furusawa 1976, Lindgren & Rowley 1977, Oshimura et al. 1976, Sakurai & Sandberg 1976, Rowley & Sandberg 1977, Rowley 1973b, 1974, Rowley & Potter 1976, Sakurai et al. 1974) and the 8; 14 translocation characteristic of Burkitt lymphoma (African and American varieties) (McCaw et al. 1977, Zech et al. 1976). Further details are indicated in the footnotes to Table 2 . From these data it can be seen that an aberration of chromosome 8 number or structure may be a component of a variety of neoplasias and hematologic disorders, and conversely several forms of leukemia may be associated with either aneuploidy or structural rearrangements.
320
RlCCARDl AND FORGASON
Table 2 Association of clinical disorders and aberrations of chromosome 8 ~~
~
~
Acquired Clinical Problem
Congenital
Other RearrangeAneuploidy ments
Trisomy
Monosomy
341 334
0
3”
12 45 0 0
Other Polycythemia Vera Sideroblastic anemia Myelodysplasia Burkitt lymphoma Anemia
512 513 8’4 0 0
Solid tumors Meningiomas Nephroblastoma Colorectal Other
0 0 419 720
Hematologic disorders Leukemias Chronic myelogenous Acute myelogenous “Acute” Eosinophilia
Totals
68
105
Trisomy
Rearrangements
Total
0 0
33 147 19 0
0 0 110 0
0 0 0 0
38 52 8 3
0 0 0 0 0
0 0 0 0 0
0 0 0 15’5 0
0 0 0 0 0
0 0 0 0 216
5 5 15 2
171’ 0 0 0
0 0 0
0 0 0
22’
222
0 118 0 123
0 0 0 0
17 1 4 12
22
3
3
2
170
16
35
8
This number includes 24 cases with acute blastic crisis (Rowley 1977, de la Chapelle et al. 1976, Engel et al. 1975, 1977, Gahrton et al. 1974, Hayata et al. 1975, Hsu et al. 1974, Lawler et al. 1975b. Mitelman et al. 1975, Prigogina & Fleischman 1975, Rowley 1973a, 1975). 2 This case also had an acquired chromosome 8 rearrangement (Hayata et al. 1975). 3 Lawler et al. (1975a) and Engel et al. (1975). 4 Includes one patient with an acquired complex rearrangement of chromosome 8 (Lindgren & Rowley 1977). Other patients had trisomy 8 as the only chromosome 8 aberration (Riccardi et al. 1978a, Yamada & Furusawa 1976, Lindgren & Rowley 1977, Jonasson et al. 1974, Lawler et al. 1975a, b, Mitelman et al. 1976, Oshimura et al. 1976, Philip 1975, Philip et al. 1977, Sakurai 8 Sandberg 1976, Rowley 8. Sandberg 1977). 5 Ford & Pittman (1974), Ford et al. (1975). 6 In addition to AML this patient also had Hodgkins disease; some cells were diploid, some showed trisomy 8 and some showed monosomy 8 (Lundh et al. 1975). 7 Yamada & Furusawa (1976), Lindgren & Rowley (1977). Oshimura et al. (1976), Sakurai & Sandberg (1976), Rowley & Sandberg (1977), Rowley (1973b, 1974). 8 This number includes two patients with myelomonocytic leukemia (de la Chapelle et al. 1976) and four patients where the diagnosis was not further specified (Rowley 1977). 9 This number includes one patient with acute myelomonocytic leukemia (Rowley 8. Potter 1976). 10 This case was specified only as acute nonlymphocytic leukemia (Gafter et al. 1976). 11 Yamada & Furusawa (1976), Weinfeld et al. (1977). 12 Rowley (1975a, b). Hsu et al. (1974), Mitelman 8 Levan (1976). 13 This number includes one patient with sideroachrestic anemia (Jonasson et al. 1974), two patients thought to have a preleukemic condition (de la Chapelle et al. 1976), and two other patients (Bitran et al. 1977 and Hellstrom et al. 1971). 14 This number includes one patient with aplastic anemia (Yamada & Furusawa 1976), one patient with thrombocytopenia and anemia (de la Chapelle et al. 1976), one patient with thrombocytopenia and granulocytopenia (de la Chapelle et al. 1976), two patients with pancytopenia (de l a Chapelle et al. 1976). two patients said to have preleukemia (Panani et al. 1977), and one patient with thrombocytosis (Rowley 1973~). 15 The characteristic abnormality was an 8q;14q translocation (McCaw et al. 1977, Zech et al. 1976). 16 This number includes one patient with sideropenic anemia (Bernsen et al. 1977), and one patient and ten of her relatives with hereditary spherocytosis segregating concordantly with a balanced reciprocal translocation 8p;12p (Kimberling et ai. 1975). 17 Monosomy 8 may also have been accompanied by monosomy 22 (Mark 1973a. b, Mark et al. 1972a, b). 1s Niss 8 Passarge (1976). 1
CHROMOSOME 8 AND NEOPLASIA
Discussion
From one extreme viewpoint, cancer may be considered to be a direct consequence of a chromosome abnormality, as for example retinoblastoma accompanying deletion of chromosome 13's band q14 (Knudson et al. 1976). At the other extreme, a chromosome abnormality may he construed as merely a coincidental irrelevant byproduct of malignant transformation. A middle-ground approach would consider that chromosomal changes reflect, and probably abet, malignant transformation (Nowell 1976, Riccardi et al. 1978a). In order to explore these possibilities, we examined the reported associations between chromosome 8 and various neoplastic and hematologic proliferative disorders. Chromosome 8 was selected because there are too many types of neoplasms linked with chromosome 8 abnormalities to allow for a simple causal relationship. By looking carefully at many reports we hoped to recognize general principles regarding the relationship of malignancy to either chromosome 8 specifically or chromosomes in general. What we know about chromosome 8 from other vantage points is not helpful; only one gene locus has been assigned to chromosome 8, i.e., glutathione reductase (de la Chapelle et al. 1976). Chromosome handing techniques applied to sorting out changes in chromosome number and structure which accompanied the development of malignancies (Oshimura et
321
al. 1976, Rowley 1973a b, Muller & Stalder 1976) led to two notable early findings: the 9;22 translocation basis of the Philadelphia chromosome and the frequent presence of trisomy 8 in abnormal cells of bone marrow of patients with various hematologic disorders, especially polycythemia Vera and CML, and AML. The essential observations regarding chromosome 8 are these (see Table 2 for references): 1. Congenital mosaic trisomy 8 may have an increased association with malignancy, since the latter was present in 3 out of 74 patients. Congenital chromosome 8 rearrangements have not been associated with neoplasia. 2. Acquired mosaic trisomy 8 is frequently associated with AML and the blastic phase of CML. Other hematologic proliferative disorders may also show this change. 3. Monosomy 8 has been noted in 17 meningiomas and has been seen in myelogenous leukemias, and nullisomy 8 has been noted in certain ovarian cancers. 4. Acquired chromosome translocations appear to be characteristic of at least two malignancies: Burkitt lymphoma [t(8q; 14q)], and AML [t(8q;21q)]. 5. Some neoplasias may be characteristically associated with more than one type of chromosome abnormality, e.g., AML with trisomy 8 and 8;21 translocations, CML with trisomy 8 and 9;22 translocations, and meningioma with monosomy 8 or 22.
This number includes at least one patient with familial polyposis coli (Baker 1968), one patient with rectal cancer, and two with colon cancers (Sonta et al. 1977). 20 This number includes one patient each with liposarcoma and teratosarcoma of the testis (Sonta et al. 1977). two patients with breast cancer (Kakati et al. 1976, Sonta et al. 1977), one patient with endometrial carcinoma (Baker 1968), one patient with ovarian adenocarcinoma (Kakati et al. 1976). and one cese of ovarian teratoma (Patil et al. 1978). 21 This represents two patients with ovarian adenocarcinoma with mosaic nullisomy 8 (Tiepolo 8 Zuffardi 1973). This number includes one patient with ovarian papillary cystadenocarcinoma (Berger & Lacour 1974), and one patient with malignant melanoma (Berger et at. 1974). 23 This is a case of rhabdomyosarcoma of the prostate (Danks & Sillence 1977). 19
**
3 22
RlCCARDl AND FORGASON
6. There are many types of neoplasia not associated with chromosome 8 abnormalities, although they may have characteristic associations with other chromosome abnormalities (Kakati et al. 1976, Rowley 1975a). Based on these observations, one general principle becomes apparent: although a given chromosome abnormality may be characteristic of a neoplasm, no chromosome abnormality is either specific, sufficient, or necessary for a neoplasm’s full natural evolution. Thus, in many instances the chromosome abnormality may represent an epiphenomenon not intrinsically required by the neoplastic process, though a chromosome abnormality may enhance the tumor’s progress and some neoplasms are abetted more by certain chromosome changes than by others. I n this context we suggest that ordinarily a chromosome abnormaIity develops during or after malignant transformation, with the net effect of enhancing the further evolution and development of the neoplasm. This hypothesis does not account for the mechanisms of enhancing the neoplasm’s developments other than to indicate that certain cells will have a growth advantage consequent to the chromosomal change. Nor does this hypothesis account for the apparently non-random nature of some of the malignancy-karyotype correlations. However, it does suggest that, except for some instances of retinoblastoma (Knudson e t al. 1976) a n d Wilms tumor (Riccardi et al. 1978b), the chromosomal change is secondary and therefore its derivation has two components which can be investigated separately: the mechanism(s) of its occurrence o n the one hand and the basis of its enhancing effect on the other. The mechanisms of occurrence are probably nonspecific, accounting for many types of chromosome abnormalities, while the effect of the chromosome change apparently enhances the tumor’s growth potential, in this
way reflecting some basic property of that type of tumor. References
Atkin, N. B. (1971). Cytogenetic aspects of malignant transformation. Exp. Biol. Med. 6, 1-171. Atkin, N. B. & V. J. Pickthall (1977). Chromosomes 1 in 14 ovarian cancers. Hum. Genet. 38, 25-33. Baker, M. C. (1968). A chromosome study of seven near-diploid carcinomas of the corpus uteri. Brit. J . Cancer 22, 683-695. Berger, R. & J. Lacour (1974). Anomalies chromosomiques dans un cancer de l’ovaire. Path. Biol. 22, 603-606. Berger, R., J. Lejeune & J. Lacour (1974). Evolution chromosomique d’un melanome malin. Rev. Europ. Etud. Clin. Biol. 16, 476-48 1. Bernsen, A. H., K. Rasmussen & J. Wielsen (1977). Trisomy 8 syndrome. Acta paediat. scand. 66, 397-402. Biederman, B. & P. Bowen (1977). De novo partial monosomy 7q in a patient with a familial balanced translocation, 46,XX,del (7)(q33)t(8;9)(qll;q31)pat. (Abstract) 1977 Birth Defects Conference, Memphis, Tennessee, June 8-10. Bitran, J., H. M. Golomb & J. D. Rowley (1977). Idiopathic acquired refractory sideroblastic anemia: Banded chromosome analysis in six patients. Acta haematol. 57, 1523. Blair, J. D. (1976). Dermatoglyphics and unusual anorectal and genital anomalies in trisomy 8 mosaicism. Birth Defects: Original Article Series Vol. XII, No. 5, 175-177. Bresson, J. L., A. Noir & M. Scherrer (1977). Deletion partielle du bras court du chromosome 8. Ann. Ge‘ne‘t. 20, 70-72. Danks, D. & D. Sillence (1977). As cited in Riccardi, V. M.: Trisomy 8: An international study of 70 patients. Birth Defects: Original Article Series Vol. X I I I , No. 3c, 171184. DeGrouchy, I., F. Josso, S. Beguin, C. Turleau, P. Jalbert & C. Laurent (1974). Deficit en facteur VII de la coagulation chez trois subjets trisomiques 8. Ann. Ge‘ne‘t. 17, 105108. de la Chapelle, A., P. Vuopio & A. k e n (1976). Trisomy 8 in the bone marrow associated with high red cell glutathione reductase activity. Blood 47, 815-826.
CHROMOSOME 8 AND NEOPLASIA
Engel, E., B. J. McGee, J. M. Flexner & S. B. Krantz (1975). Chromosome band analysis in 19 cases of chronic myeloid leukemia: 9 chronic, 10 blastic, 2 with Ph1(22q-) translocation on 17 short arm. Ann. Gin&. 18, 239-240. Engel, E., B. J. McGee, B. J. Meyers, J. M. Flexner & S. B. Krantz (1977). Chromosome banding patterns of 49 cases of chronic myelocytic leukemia. N e w Engl. J . M e d . 296, 1295. Ford, J. H. & S. M. Pittman (1974). Duplication of 21 or 8/21 translocation in acute leukemia. Lancet ii, 1458. Ford, J. H., S. M. Pittman, S. Singh, E. J. Wass, P. C. Vincent & F. W. Gunz (1975). Cytogenetic basis of acute myeloid leukemia. J . nut. Cancer Inst. 55, 761-765. Fried, K., M. Rosenblatt & G. Mundel (1977). De novo balanced reciprocal translocation 46,XY,t(6;8)(913;q22). J . med. Genet. 14, 142-144. Fryns, V. P., H. Verresen & H. Van den Berghe (1974). Partial trisomy 8: Trisomy of the distal part of the long arm of chromosome number 8+(8q2) in a severely retarded and mallformed girl. Hum. Genet. 24, 241-246. Fujimoto, A., M. G. Wilson & J. W. Towner (1975). Familial inversion of chromosome no. 8. An affected child and a carrier fetus. Hum. Genet. 27, 67-73. Gafter, U., F. Shabtai, Y . Kahn, I. Halbrecht & M. Djaldetti (1976). Aplastic anemia followed by leukemia in congenital trisomy 8 mosaicism. Clin. Genet. 9, 134-142. Gahrton, G.,J. Lindsten & L. Zech (1974). Involvement of chromosomes 8, 9, 19 and 22 in Ph1 positive and Phi negative chronic myelocytic leukemia in the chronic or blastic stage. Acta med. scand. 196, 355-360. Gellis, A. S., M. Feingold, S. B. Cassidy, B. J. McGee & E. Engel (1975). Trisomy 8 syndrome. Anier. J . Dis. Child. 129, 951-952. Giovanella, B. C . , J. S. Stehlin, C. Santamaria, S. 0. Yim, A. C. Morgan, L. J. Williams, Jr., A. Leibovitz, P. J. Fialkow & D. M. Mumford (1976). Human neoplastic and normal cells in tissue culture. I-cell lines derived from malignant melanomas and normal melanocytes. J . nut. Cancer Inst. 56, 1131-1138. Guanti, G., G. Mollica, L. Polimeno & F. Maritato (1976). rDNA and acrocentric chromosomes in man. I. rDNA levels in a subject carrier of a 8p113p translocation and
323
in his unbalanced son, Hum. Genet. 33, 103-107. Gunz, F. W., B. I. Bach, P. E. Crossen, J. E. L. Mellor, S. Singh & P. C. Vincent (1973). Relevance of the cytogenetic status in acute leukemia in adults. J . nut. Cancer Inst. 50, 55-61. Hart, J. S., J. M. Trujillo, E. J . Freireich, S. L. George & E. Frei (1971). Cytogenetic studies and their clinical correlates in adults with acute leukemia. Ann. int. M e d . 75, 353-360. Hayata, I., M. Sakurai, S. Kakati & A. A. Sandberg (1975). Chromosomes and causation of human cancer and leukemia. XVI. Banding studies of chronic myelocytic leukemia, including five unusual Phl translocations. Cancer 36, 1177-1191. Hellstrom, K., L. Hagenfeldt, A. Larson, J. Lindsten, P. Sundelin & L. Tiepolo (1971). An extra C chromosome and various metabolic abnormalities in the bone marrow from a patient with refractory sideroblastic anemia. Scund. J . Haematol. 8, 923-930. Herva, R. & A. de la Chapelle (1976). A large pericentric inversion of human chromosome 8. Amer. J . hum. Genet. 28, 208212. Hook, E. B., N. H. Hatcher & 0. H. Calka (1975). Apparent “in situ” clone of cytogenetically marked ataxia-telangectasia lymphocytes. Hum. Genet. 30, 251-257. Hsu, L. Y. F., A. V. Alter & K. Hirschhorn (1974). Trisomy 8 in bone marrow of patients with polycythemia Vera and myelogenous leukemia. Clin. Genet. 6 , 258-264. Jonasson, J., G. Gahrton, J. Lindsten, C. Simonson-Lindemalm & L. Zech (1974). Trisomy 8 in acute myeloblastic leukemia and sideroachrestic anemia. Blood 43, 557-563. Kakati, S., M. Oshimura & A. A. Sandberg (1976). The chromosomes and causation of human cancer and leukemia, XIX. Common markers in various tumors. Cancer 38, 770777. Kawana, S., G. Watanabe, T. Asami, T. Okata & M. Yamamoto (1976). Pericentric inversion of chromosome No. 8. Tolioku J . exp. M e d . 119, 65-70. Kimberling, W. J., T. Fulbeck, L. Dixon & H. A. Lubs (1975). Localization of spherocytosis to chromosome 8 or 12 and report of a family with spherocytosis and a reciprocal translocation. A m e r . J . hum. Genet. 27, 586-594. Knudson, A. G., Jr., A. T. Meadows, W. W.
324
RlCCARDl AND FORGASON
Nichols & R. Hill (1976). Chromosomal deletion and retinoblastoma. N e w Engl. J . M e d . 295, 1120-1123. Kondo, I. (1976). Two cases of trisomy 8 mosaicism. f a p . J . hum. Genet. 21, 5-11. Koszyolanyi, G.,E. M. Buhler, P. Elmiger & G. R. Stalder (1976). Trisomy 8 mosaicism. Europ. J . Pediat. 123, 293-300. Ladda, R., L. Atkins, J. Littlefield, P. Neurath & K. M. Marimuthu (1974). Computer-assisted analysis of chromosomal abnormalities: Detection of a deletion in aniridiai Wilms’ tumor syndrome. Science 185, 784787. Lawler, S. D., D. S. Lobb & E. Wiltshaw (1975a). Philadelphia-chromosome positive bone marrow cells showing loss of the Y in males with chronic myeloid leukemia. Brit. J . Haemafol. 27, 247-252. Lawler, S. D., L. M. Secker-Walker, B. M. Summersgill, B. R. Reeves, J. Lewis, H. E. M. Kay & R. M. Hardisty (1975b). Chromosome banding studies in acute leukemia at diagnosis. Scand. J . Haernatol. 15, 312-320. Levan, G. & F. Mitelman (1975). Clustering of aberrations to specific chromosomes in human neoplasms. Hereditas (Lund) 79, 156-160. Lin, C. C., I. Uchida, M. Hotz, R. C. Miller, A. E. Greene & L. L. Coriell (1975). An (8;12) translocation, balanced, 46 chromosomes. Cytogenet. Cell Genet. 14, 78-79. Lindgren, V. & J. D. Rowley (1977). Comparable complex rearrangements involving 8:21 and 9;22 translocations in leukemia. Nature 266, 744-745. Linman, J. W. & G. C. Bagby (1976). The preleukemic syndrome: Clinical and laboratory features, natural course and management. Blood Cells 2, 11-31. Lundh, B., F. Mitelman, P. G. Nilsson, M. Stenstam & N. Soderstrom (1975). Chromosome abnormalities identified by banding technique in a patient with acute myeloid leukemia complicating Hodgkin’s disease. Scand. J . Haematol. 14, 303-307. Mark, J. (1973a). Origin of the ring chromosome in a human recurrent meningioma studied with G-band technique. Acta path. microbiol. scund. Sect. A 81, 588-590. Mark, J. (1973b). Karyotype patterns in human meningiomas. A comparison between studies with G- and Q-banding techniques. Hereditas (Lund) 75, 213-220. Mark, J., F. Mitelman & G. Levan (1972a). On the specificity of the G abnormality in
human meningiomas. Acta path. microbiol. scund. Sect. A 80, 812-820. Mark, J., F. Mitelman & G. Levan (1972b). Identification by fluorescence of the G chromosome lost in human meningiomas. Hereditas (Lund) 71, 163-168. McCaw, B. K., A. L. Epstein, H. S. Kaplan & F. Hecht (1977). Chromosome 14 translocations in African and North American Burkittt’s lymphoma. Znt. J . Cancer 19, 482-486. Mitelman, F. (1974). Heterogeneity o’f Phl in chronic myeloid leukemia. Hereditas (Lund) 76, 315-316. Mitelman, F. & G. Levan (1976). Clustering of aberrations t o specific chromosomes in human neuplasms. 11. A survey of 287 neoplasms. Hereditas (Lund) 82, 167-174. Mitelman, F., J. Mark, P. G. Nilsson, H. Dencker, C. Norryd & K. G. Tranberg (1974). Chromosome banding pattern in a human colonic polyps. Hereditas (Lund) 78, 63-68. Mitelman, F., P. G. Nilsson & L. Brandt (1975). Abnormal clones resembling those seen in blast crisis arising in the spleen in chronic myelocytic leukemia. J . nut. Cancer Znst. 54, 1319-1320. Mitelman, F., P. G. Nilsson, G. Levan & L. Brandt (1976). Non-random chromosome changes in acute myeloid leukemia. Chromosome banding examination of 30 cases at diagnosis. Int. J . Cancer 18, 31-38. Muller, H. & G. R. Stalder (1976). Chromosomes and human neoplasms. Achievements using new staining techniques. Europ. J . Pediat. 123, 1-13. Niebuhr, E. (1973). A familial translocation t(6q+ ;8q-) identified by fluorescence microscopy. Hum. Genet. 18, 189-192. Niss, R. & E. Passarge (1976). Trisomy 8 restricted t o cultered fibroblasts. J . m e d . Genet. 13, 229-234. Nowell, P. C. (1976). The clonal evolution of tumor cell populations. Science 194, 23-28. Nowell, P. C. & D. A. Hungerford (1960). A minute chromosome in human chronic granulocytic leukemia. Science 132, 197-198. Orye, E. & M. Craen (1976). A new chromosome deletion syndrome. Report of a patient with 46,XY,8p - chromosome constitution. Clin. Genet. 9, 289-301. Oshimura, M., I. Hayata, S. Kakati & A. A. Sandberg (1976). Chromosomes and causation of human cancer and leukemia. XVII.
CHROMOSOME 8 AND NEOPLASIA
Banding studies in acute myeloblastic Ieukemia (AML). Cancer 38, 748-761. Panani, A., A. G. Papayannis, K. Kyrkou & C. Gardikas (1977). Cytogenetic studies in preleukemia using the G-banding staining technique. Scand. J . Haemntol. 18, 301-308. Patil, S., B. K. McCaw, F. Hecht, D. Linder & E. Lovrien (1978). Human benign ovarian teratomas: chromosomal and electrophoretic enzyme studies. Birth Defects: Original Article Series, Vol. X l V , No. 6b, 297-301. Philip, P. (1975). Trisomy 8 in acute myeloid leukemia. Scand. J . Haematol. 14, 14@-147. Philip, P., G . L. Wantzin, M. K. Jensen & A. Drivsholm (1977). Trisomy 8 in acute myeloid leukemia: A non-random event. Scand. J . Haonatol. 18, 163-169. Prigogina, E. L. & E. W. Fleischman (1975). Certain patterns of karyotype evolution in chronic myelogeneous leukemia. Hum. Genet. 30, 113-119. Reiss, J. A,, P. Brenes, R. E. Magenis & J. Chamberlin (1977). The 8p - syndrome. (Abstract). 1977 Birth Defects Conference, Memphis, Tennessee, June 8-10. Rethore, M., A. Aurias, J. Couturier, B. Dutrillaux, M. Prieur & J. Lejuene (1977). Chromosome 8: Complete et Trisomies Segmentaires. Ann. Gknkt. 20, 5-11. Riccardi, V. M. (1977). Trisomy 8: An international study of 70 patients. Birth Defects: Original Article Series Vol. X l I l , No. 312, 171-184. Riccardi, V. M., J. Humbert & D. Peakman (1978a). Acute leukemia associated with trisomy 8 mosaicism and a familial translocation 46,XY,t(7;20)(~13;~12).Amer. J . med. Genet. 2, 15-21. Riccardi, V. M., E. Sujansky, A. C. Smith & U. Francke (1978b). Chromosomal imbalance in the aniridia-Wilms tumor association: l l p interstitial deletion. Pediatrics 61, 604-610. Rodewald, A., S. Stengel-Rutkowski, P. Schulz & H. Cleve (1977). Partial monosomy 8p. An attempt to establish a new chromosome deletion syndrome. Europ. J . Pediat. 125, 45-57. Rosenthal, I. M., E. Krrnpotic, M. Bocian & K. Szego (1973). Trisomy of the short arm of chromosome 8: Association with translocation between chromosomes 8 and 22, 46,XY,22 - ,t(8p;22q)+. Clin. Genet. 4, 507516. Rowley, J. D. (1973a). A new consistent chromosomal abnormality in chronic mye-
325
logenous leukemia identified by quinacrine fluorescence and Giemsa staining. Nature 243, 290-293. Rowley, J. D. (1973b). Identification of a translocation with quinacrine fluorescence in a patient with acute leukemia. Ann. Genet. 16, 109-112. Rowley, J. D. (1973~).Acquired trisomy 9. Lancet ii, 390. Rowley, J. D. (1974). Missing sex chromosomes and translocations in acute leukemia. Lancet ii, 835-836. Rowley, J. D. (1975a). Non-random chromosomal abnormalities in hematologic disorders of man. Proc. nut. Acad. Sci (Wash.) 72, 152-156. Rowley, J. D. (1975b). Abnormalities of chromosome 1 in myeloproliferative disorders. Cancer 36, 1748-1758. Rowley, J. D. (1977). Population cytogenetics of leukemia. Population Cytogenetics Studies in Humans, ed. Hook, E. B. & 1. H. Porter. New York, Academic Press Inc pp. 189-216. Rowley, I. D. & D. Potter (1976). Chromosomal banding patterns in acute non-lymphocytic leukemia. Blood 47, 705-721. Rowley, J. D. & A. A. Sandberg (1977). Personal communications corroborating and clarifying cited data. Sakurai, M. & A. A. Sandberg (1976). Chromosomes and causation of human cancer and leukemia. XI. Correlation of karyotypes with clinical features of acute myeloblastic leukemia. Cancer 37, 285-299. Sakurai, M., M. Oshimura, S. Kakati & A. A. Sandberg (1974). 8-21 translocation and missing sex chromosomes in acute leukemia. Lancet ii, 227-228. Sanchez, 0. & J. J. Yunis (1974). Partial trisomy 8 (8q24) and the trisomy-8 syndrome. Hum. Genet. 23, 297-303. Schinzel, A. (1977). Partial trisomy 8 in halfsisters with distinct dysmorphic patterns not similar to the trisomy 8 mosaicism syndrome. Hum. Genet. 37, 17-26. Sonta, S., M. Oshimura, J. T. Evans & A. A. Sandberg (1977). Chromosomes and causation of human cancer and leukemia. XX. Banding patterns of primary tumors. J . nut. Cancer Inst. 58, 49-53. Taillemete, J. L., J. Channarond, H. Tinel, W. Mulliez & C. Roux (1975). Deletion partielle du bras court du chromosome 8. Ann. Ge'nkt. 18, 251-255. Tiepolo, L. & 0. Zuffardi (1973). Identifica-
326
RlCCARDl AND FORGASON
tion of normal and abnormal chromosomes in tumor cells. Cytogenct. Cell Genet. 12, 8-16. Weinfeld, A., J. Westin & B. Swolin (1977). Ph1-negative eosinophilic leukemia with trisomy 8. Scand. J . Haematol. 18, 413-420. Weleber, R. G., R. S. Verma, W. J. Kimberling, H. G. Fieger, Jr. & H. A. Lubs (1976). Duplication-deficiency of the short arm of chromosome 8 following artificial insemination. Ann. Genet. 19, 241-247. Wurster-Hill, D. H. & D. Hoefnagel (1974). Banding identification of partial trisomy 15 of 8/21 translocation. J . ment. D e f . Res. 18, 139-144. Yamada, K. & S. Furusawa (1976). Preferential involvement of chromosomes no. 8 and no. 21 in acute leukemia and preleukemia. Blood 47, 679-686.
Yanagisawa, S. (1973). Partial trisomy 8: Further observation of a familial C/G translocation chromosome identified by the Qstaining methods. J . ment. Defic. Res. 17, 28-32. Zech, L., U. Haglund, K. Nilsson & G. Klein (1976). Characteristic chromosomal abnormalities in biopsies and lymphoid cell lines lfrom patients with Burkitt and nonBurkitt lymphomas. Int. J . Cancer 17, 47-56. Address: Vincent M . Riccardi, M . D . Klcberg Genetics Center Baylor College of Medicine Texas Medical Center Houston, Texas 77030 U .S . A .
Chromosome 8 abnormalities as components of neoplastic and hematologic disorders VINCENT M. RICCARDI AND JUDY FORGAS'ON
Kleberg Genetics Center, Baylor College of Medicine, Texas Medical Center, Houston, Texas, U. S. A. Publications involving patients with any abnormality of chromosome 8 have been reviewed in detail. For the time period involved, a total of 277 cases were found, including 74 instances of congenital aneuploidy, 130 instances of acquired aneuploidy, 38 instances of congenital rearrangements, and 35 instances of acquired rearrangements. A total of 170 cases of neoplastic and hematologic disorders were included; three were associated with congenital aneuploidy, two with congenital rearrangements, and the remaining 165 with acquired aberrations. The specific disorders ranged from sideroblastic anemia through chronic and acute leukemia to solid tumors. There appears to be a definite, though nonspecific correlation between congenital or acquired chromosome 8 abnormalities and the development of certain types of neoplastic growth. Received 30 May, revised 2 November, accepted for publication 17 November 1978 K e y words: Cancer; chromosome 8; leukemia; neoplasia.
Increasingly, both benign and malignant neoplasia are being considered in genetic terms. Chromosomes, as units of organization of the cell's genetic material, have become especially important in our efforts t o understand the etiology, pathogenesis, and natural history of various types of neoplasia, including cancer (Atkin 1971, Nowell 1976, Rowley 1977). I n some instances chromosome aberrations clearly seem to cause tumors (e.g., chromosome 13 long arm deletions and retinoblastomas (Knudson et al. 1976)), while in most other instances it is not clear whether associated chromosome aberrations cause the neoplasm, a r e conssquences of the malignant transformation process(es), or are merely
incidental accompaniments. T h e best known association of cancer with chromosome derangement is that of chronic myelogenous leukemia (CML) and the Philadelphia chromosome (Nowell & Hungerford 1960, Mitelman 1974). Among the other recognized associations, perhaps the potentially most informative involve chromosome 8 because several types of abnormalities have been noted in a variety of malignancies. Starting from our previous interests in the consequences of congenital trisomy 8 and terminal 8q triplications (Riccardi 1977), we have reviewed published data dealing with known aberrations of chromosome 8 and their associations with neoplasia.
0009-9163/79/040317-10 $02.50/0 0 1979 Munksgaard, Copenhagen
31 8
RlCCARDl AND FORGASON
Materials and Methods
Individual case reports and reviews through July 1977 were ascertained by utilizing standard medical and biological reference indices, as well as a computerized literature search. The index topics were “human chromosome 8”, “chromosomes and malignancy”, and “chromosomes and hematologic disorders”. All articles that included at least one case with a chromosome 8 aberration were abstracted. In some instances an author of a paper was personally contacted to clarify or update the published data. Only those studies which utilized chromosome banding techniques were included. Additional articles dealing with other chromosomal anomalies in neoplasia were reviewed t o provide a context for appreciating the relative role of chromosome 8 in neoplastic disorders (Atkin 1971, Atkin & Pickthall 1977, Giovanella et al. 1976, Gunz et al. 1973, Hart et al. 1971, Levan & Mitelman 1975, Rowley 1975b), but no effort was made to determine the proportion of chromosome 8 aberrations either among all neoplasias or among chromosomally abnormal neoplasias. Methodologic problems were of three types: 1. Inclusion of the same patient or groups of patients in sequential reports and reviews, without intrinsic mechanisms for clarification; 2 . Failure of many authors to associate specific cytogenetic findings with specific patients; and 3. Many instances where a chromosome 8 abnormality was only one of several cytogenetic aberrations. The first two problems were handled by careful cross-checking and by inquiries of selected authors. The third problem was handled by our decision to include the case as an instance of chromosome 8 abnormalities whether or not other chromosomes
were involved. In those instances of congenital chromosome 8 aberrations where multiple family members were involved, only one case per family was tallied. The term “acquired chromosome abnormality” indicates that the chromosome abnormality was not congenital and that it evolved within the neoplastic cell population (with one exception (Riccardi et al. 1978a)). Although purely inferential, this definition is supported by investigations on the “premalignant” state (Linman & Bagby 1976, Panani et al. 1977), and certain heritable disorders predisposing to leukemia (Hook et al. 1975). Results
As indicated in Table 1 , we ascertained 277 cases with either a missing, extra, deleted, translocated, or otherwise abnormal chromosome 8. In 112 cases the chromosome abnormality was congenital, involving either trisomy (almost always mosaic) or rearrangements, balanced or unbalanced. As seen in Table 2, three patients with congenital trisomy 8 were found to have a malignancy: acute non-lymphocytic leukemia (Gafter et al. 1976), Wilms tumor (Niss & Passarge 1976) and prostatic rhahdomyosarcoma (Danks & Sillence 1977). One patient with a translocation had a Wilms tumor (Ladda et al. 1974), although the complex chromosome rearrangement actually involves a net loss of a portion of I l p (Francke, U. & Riccardi, V. M., unpublished data) and thus will not be included here. Two congenital translocation patients had distinctive anemias. Most of the patients with congenital chromosome 8 defects were young children, and many had died as youngsters, perhaps before a neoplastic diathesis could he manifest. The remaining 165 cases (Table 1) had acquired chromosome 8 abnormalities, recognized as part of evaluations for hemato-
CHROMOSOME 8 AND NEOPLASIA Table 1 Types of chromosome 8 aberrations and numbers ascertained No. ascertained Acquired aberrations Aneuploidy Rearrangements
130’ 352
Congenital aberrations Aneuploidy Rearrangements
743 384
Total aberrations
165
112
277
Rowley (1977, 1975b), Riccardi et al. (1978a), Panani et al. (19771, Yamada & Furusawa (1976), Lindgren & Rowley (1977). Jonasson et al. (1974), Lawler et al. (1975a, b), Mitelman et al. (1976), Oshimura et al. (1976), Philip (1975), Philip et al. (1977), Sakurai & Sandberg (1976), Rowley & Sandberg (1977). de la Chapelle et al. (1976), Engel et al. (1975, 1977), Gahrton et at. (1974). Hayata et al. (1975). Hsu et al. (1974). Mitelman et al. (1975), Prigogina & Fleischman (1975), Rowley (1973a), Mitelrnan et al. (1974), Baker (1968), Patil et al. (1978), Sonta et al. (1977), Mark (1973a, b), Mark et al. (1972a, b), Ford 8 Pittman (1974), Ford et al. (1975), Tiepolo 8 Zuffardi (19731, Rowley (1973~).Weinfeld et al. (1977), Mitelman & Levan (1976). Bitran et al. (1977). Helistrom et al. (1971). Yamada & Furusawa (1976), Lindgren 8. Rowley (1977). Lawler et al. (1975a), Oshimura et al. (1976), Sakurai & Sandberg (1976), Engel et al. (1975), Rowley (1973b, 1974), Sakurai et al. (1974), McCaw et al. (1977), Zech et al. (1976), Berger et al. (1974), Berger & Lacour (1974). 3 Riccardi (1977), Bernsen et al. (1977). Blair (1976), Gafter et al. (1976), Gellis et al. (1975), Koszyolanyi et al. (19761, Niss & Passarge (1976). DeGrouchy et al. (1974), Kondo (1976). Danks & Sillence (1977). Riccardi (1977). Kirnberling et al. (1975), Biederrnan Bowen (1977), Fried et al. (1977), Herva 8 de la Chapelle (1976), Kawana e t al. (1976). Bresson et al. (1977), Sanchez 8 Yunis (1974), Fryns et al. (1974), Fujimoto et al. (1975), Ladda et al. (1974), Orye & Craen (1976). Reiss et al. (1977), Rethore et al. (1977), Rodewald et al. (1977), Rosenthal et al. (1973), Schinzel (1977). Taillemete et ai. (1975). Weleber et al. (1976), Wurster-Hill & Hoefnagel (1974), Yanagisawa (1973), Guanti et al. (1976), Lin er al. (1975), Niebuhr (1973).
logic or neoplastic disorders. Aneuploidy was noted 130 times, including trisomy 8 in 105 instances, while rearrangements accounted for 35 cases. As summarized in Table 2 , among the trisomy 8 cases 6 4 % (67 out of 105) were
319
seen in association with AML (Riccardi et al. 1978a, Yamada & Furusawa 1976, Lindgren & Rowley 1977, Jonasson et al. 1974, Lawler et al. 1975a, Mitelman et al. 1976, Oshimura et al. 1976, Philip 1975, Philip et al. 1977, Sakurai & Sandberg 1976, Rowley & Sandberg 1977) and the blastic phase of CML (Rowley 1977, de la Chapelle et al. 1976, Engel et al. 1975, 1977, Gahrton et al. 1974, Hayata et al. 1975, Hsu et al. 1974, Lawler et al. 1975b, Mitelman et al. 1975, Prigogina & Fleischman 1975, Rowley 1973a, 1975a). and 1070 (11 out of 105) were seen in solid tumor cells, most notably colorectal cancers (Kakati et al. 1976, Mitelman et al. 1974, Baker 1968, Patil et al. 1978, Sonta et al. 1977). Monosomy 8 was associated with meningiomas (17 times) (Mark 1973a, b, Mark et al. 1972a, b) but was also noted five times in AML and CML (Hayata et al. 1975, Ford & Pittman 1974, Ford et al. 1975). In the “other aneuploidy” category, two ovarian adenocarcinomas (from two separate patients) showed mosaic nullisomy 8 (Tiepolo & Zuffardi 1973). The most distinctive acquired rearrangements were the 8;21 translocation characteristic of AML (Yamada & Furusawa 1976, Lindgren & Rowley 1977, Oshimura et al. 1976, Sakurai & Sandberg 1976, Rowley & Sandberg 1977, Rowley 1973b, 1974, Rowley & Potter 1976, Sakurai et al. 1974) and the 8; 14 translocation characteristic of Burkitt lymphoma (African and American varieties) (McCaw et al. 1977, Zech et al. 1976). Further details are indicated in the footnotes to Table 2 . From these data it can be seen that an aberration of chromosome 8 number or structure may be a component of a variety of neoplasias and hematologic disorders, and conversely several forms of leukemia may be associated with either aneuploidy or structural rearrangements.
320
RlCCARDl AND FORGASON
Table 2 Association of clinical disorders and aberrations of chromosome 8 ~~
~
~
Acquired Clinical Problem
Congenital
Other RearrangeAneuploidy ments
Trisomy
Monosomy
341 334
0
3”
12 45 0 0
Other Polycythemia Vera Sideroblastic anemia Myelodysplasia Burkitt lymphoma Anemia
512 513 8’4 0 0
Solid tumors Meningiomas Nephroblastoma Colorectal Other
0 0 419 720
Hematologic disorders Leukemias Chronic myelogenous Acute myelogenous “Acute” Eosinophilia
Totals
68
105
Trisomy
Rearrangements
Total
0 0
33 147 19 0
0 0 110 0
0 0 0 0
38 52 8 3
0 0 0 0 0
0 0 0 0 0
0 0 0 15’5 0
0 0 0 0 0
0 0 0 0 216
5 5 15 2
171’ 0 0 0
0 0 0
0 0 0
22’
222
0 118 0 123
0 0 0 0
17 1 4 12
22
3
3
2
170
16
35
8
This number includes 24 cases with acute blastic crisis (Rowley 1977, de la Chapelle et al. 1976, Engel et al. 1975, 1977, Gahrton et al. 1974, Hayata et al. 1975, Hsu et al. 1974, Lawler et al. 1975b. Mitelman et al. 1975, Prigogina & Fleischman 1975, Rowley 1973a, 1975). 2 This case also had an acquired chromosome 8 rearrangement (Hayata et al. 1975). 3 Lawler et al. (1975a) and Engel et al. (1975). 4 Includes one patient with an acquired complex rearrangement of chromosome 8 (Lindgren & Rowley 1977). Other patients had trisomy 8 as the only chromosome 8 aberration (Riccardi et al. 1978a, Yamada & Furusawa 1976, Lindgren & Rowley 1977, Jonasson et al. 1974, Lawler et al. 1975a, b, Mitelman et al. 1976, Oshimura et al. 1976, Philip 1975, Philip et al. 1977, Sakurai 8 Sandberg 1976, Rowley 8. Sandberg 1977). 5 Ford & Pittman (1974), Ford et al. (1975). 6 In addition to AML this patient also had Hodgkins disease; some cells were diploid, some showed trisomy 8 and some showed monosomy 8 (Lundh et al. 1975). 7 Yamada & Furusawa (1976), Lindgren & Rowley (1977). Oshimura et al. (1976), Sakurai & Sandberg (1976), Rowley & Sandberg (1977), Rowley (1973b, 1974). 8 This number includes two patients with myelomonocytic leukemia (de la Chapelle et al. 1976) and four patients where the diagnosis was not further specified (Rowley 1977). 9 This number includes one patient with acute myelomonocytic leukemia (Rowley 8. Potter 1976). 10 This case was specified only as acute nonlymphocytic leukemia (Gafter et al. 1976). 11 Yamada & Furusawa (1976), Weinfeld et al. (1977). 12 Rowley (1975a, b). Hsu et al. (1974), Mitelman 8 Levan (1976). 13 This number includes one patient with sideroachrestic anemia (Jonasson et al. 1974), two patients thought to have a preleukemic condition (de la Chapelle et al. 1976), and two other patients (Bitran et al. 1977 and Hellstrom et al. 1971). 14 This number includes one patient with aplastic anemia (Yamada & Furusawa 1976), one patient with thrombocytopenia and anemia (de la Chapelle et al. 1976), one patient with thrombocytopenia and granulocytopenia (de la Chapelle et al. 1976), two patients with pancytopenia (de l a Chapelle et al. 1976). two patients said to have preleukemia (Panani et al. 1977), and one patient with thrombocytosis (Rowley 1973~). 15 The characteristic abnormality was an 8q;14q translocation (McCaw et al. 1977, Zech et al. 1976). 16 This number includes one patient with sideropenic anemia (Bernsen et al. 1977), and one patient and ten of her relatives with hereditary spherocytosis segregating concordantly with a balanced reciprocal translocation 8p;12p (Kimberling et ai. 1975). 17 Monosomy 8 may also have been accompanied by monosomy 22 (Mark 1973a. b, Mark et al. 1972a, b). 1s Niss 8 Passarge (1976). 1
CHROMOSOME 8 AND NEOPLASIA
Discussion
From one extreme viewpoint, cancer may be considered to be a direct consequence of a chromosome abnormality, as for example retinoblastoma accompanying deletion of chromosome 13's band q14 (Knudson et al. 1976). At the other extreme, a chromosome abnormality may he construed as merely a coincidental irrelevant byproduct of malignant transformation. A middle-ground approach would consider that chromosomal changes reflect, and probably abet, malignant transformation (Nowell 1976, Riccardi et al. 1978a). In order to explore these possibilities, we examined the reported associations between chromosome 8 and various neoplastic and hematologic proliferative disorders. Chromosome 8 was selected because there are too many types of neoplasms linked with chromosome 8 abnormalities to allow for a simple causal relationship. By looking carefully at many reports we hoped to recognize general principles regarding the relationship of malignancy to either chromosome 8 specifically or chromosomes in general. What we know about chromosome 8 from other vantage points is not helpful; only one gene locus has been assigned to chromosome 8, i.e., glutathione reductase (de la Chapelle et al. 1976). Chromosome handing techniques applied to sorting out changes in chromosome number and structure which accompanied the development of malignancies (Oshimura et
321
al. 1976, Rowley 1973a b, Muller & Stalder 1976) led to two notable early findings: the 9;22 translocation basis of the Philadelphia chromosome and the frequent presence of trisomy 8 in abnormal cells of bone marrow of patients with various hematologic disorders, especially polycythemia Vera and CML, and AML. The essential observations regarding chromosome 8 are these (see Table 2 for references): 1. Congenital mosaic trisomy 8 may have an increased association with malignancy, since the latter was present in 3 out of 74 patients. Congenital chromosome 8 rearrangements have not been associated with neoplasia. 2. Acquired mosaic trisomy 8 is frequently associated with AML and the blastic phase of CML. Other hematologic proliferative disorders may also show this change. 3. Monosomy 8 has been noted in 17 meningiomas and has been seen in myelogenous leukemias, and nullisomy 8 has been noted in certain ovarian cancers. 4. Acquired chromosome translocations appear to be characteristic of at least two malignancies: Burkitt lymphoma [t(8q; 14q)], and AML [t(8q;21q)]. 5. Some neoplasias may be characteristically associated with more than one type of chromosome abnormality, e.g., AML with trisomy 8 and 8;21 translocations, CML with trisomy 8 and 9;22 translocations, and meningioma with monosomy 8 or 22.
This number includes at least one patient with familial polyposis coli (Baker 1968), one patient with rectal cancer, and two with colon cancers (Sonta et al. 1977). 20 This number includes one patient each with liposarcoma and teratosarcoma of the testis (Sonta et al. 1977). two patients with breast cancer (Kakati et al. 1976, Sonta et al. 1977), one patient with endometrial carcinoma (Baker 1968), one patient with ovarian adenocarcinoma (Kakati et al. 1976). and one cese of ovarian teratoma (Patil et al. 1978). 21 This represents two patients with ovarian adenocarcinoma with mosaic nullisomy 8 (Tiepolo 8 Zuffardi 1973). This number includes one patient with ovarian papillary cystadenocarcinoma (Berger & Lacour 1974), and one patient with malignant melanoma (Berger et at. 1974). 23 This is a case of rhabdomyosarcoma of the prostate (Danks & Sillence 1977). 19
**
3 22
RlCCARDl AND FORGASON
6. There are many types of neoplasia not associated with chromosome 8 abnormalities, although they may have characteristic associations with other chromosome abnormalities (Kakati et al. 1976, Rowley 1975a). Based on these observations, one general principle becomes apparent: although a given chromosome abnormality may be characteristic of a neoplasm, no chromosome abnormality is either specific, sufficient, or necessary for a neoplasm’s full natural evolution. Thus, in many instances the chromosome abnormality may represent an epiphenomenon not intrinsically required by the neoplastic process, though a chromosome abnormality may enhance the tumor’s progress and some neoplasms are abetted more by certain chromosome changes than by others. I n this context we suggest that ordinarily a chromosome abnormaIity develops during or after malignant transformation, with the net effect of enhancing the further evolution and development of the neoplasm. This hypothesis does not account for the mechanisms of enhancing the neoplasm’s developments other than to indicate that certain cells will have a growth advantage consequent to the chromosomal change. Nor does this hypothesis account for the apparently non-random nature of some of the malignancy-karyotype correlations. However, it does suggest that, except for some instances of retinoblastoma (Knudson e t al. 1976) a n d Wilms tumor (Riccardi et al. 1978b), the chromosomal change is secondary and therefore its derivation has two components which can be investigated separately: the mechanism(s) of its occurrence o n the one hand and the basis of its enhancing effect on the other. The mechanisms of occurrence are probably nonspecific, accounting for many types of chromosome abnormalities, while the effect of the chromosome change apparently enhances the tumor’s growth potential, in this
way reflecting some basic property of that type of tumor. References
Atkin, N. B. (1971). Cytogenetic aspects of malignant transformation. Exp. Biol. Med. 6, 1-171. Atkin, N. B. & V. J. Pickthall (1977). Chromosomes 1 in 14 ovarian cancers. Hum. Genet. 38, 25-33. Baker, M. C. (1968). A chromosome study of seven near-diploid carcinomas of the corpus uteri. Brit. J . Cancer 22, 683-695. Berger, R. & J. Lacour (1974). Anomalies chromosomiques dans un cancer de l’ovaire. Path. Biol. 22, 603-606. Berger, R., J. Lejeune & J. Lacour (1974). Evolution chromosomique d’un melanome malin. Rev. Europ. Etud. Clin. Biol. 16, 476-48 1. Bernsen, A. H., K. Rasmussen & J. Wielsen (1977). Trisomy 8 syndrome. Acta paediat. scand. 66, 397-402. Biederman, B. & P. Bowen (1977). De novo partial monosomy 7q in a patient with a familial balanced translocation, 46,XX,del (7)(q33)t(8;9)(qll;q31)pat. (Abstract) 1977 Birth Defects Conference, Memphis, Tennessee, June 8-10. Bitran, J., H. M. Golomb & J. D. Rowley (1977). Idiopathic acquired refractory sideroblastic anemia: Banded chromosome analysis in six patients. Acta haematol. 57, 1523. Blair, J. D. (1976). Dermatoglyphics and unusual anorectal and genital anomalies in trisomy 8 mosaicism. Birth Defects: Original Article Series Vol. XII, No. 5, 175-177. Bresson, J. L., A. Noir & M. Scherrer (1977). Deletion partielle du bras court du chromosome 8. Ann. Ge‘ne‘t. 20, 70-72. Danks, D. & D. Sillence (1977). As cited in Riccardi, V. M.: Trisomy 8: An international study of 70 patients. Birth Defects: Original Article Series Vol. X I I I , No. 3c, 171184. DeGrouchy, I., F. Josso, S. Beguin, C. Turleau, P. Jalbert & C. Laurent (1974). Deficit en facteur VII de la coagulation chez trois subjets trisomiques 8. Ann. Ge‘ne‘t. 17, 105108. de la Chapelle, A., P. Vuopio & A. k e n (1976). Trisomy 8 in the bone marrow associated with high red cell glutathione reductase activity. Blood 47, 815-826.
CHROMOSOME 8 AND NEOPLASIA
Engel, E., B. J. McGee, J. M. Flexner & S. B. Krantz (1975). Chromosome band analysis in 19 cases of chronic myeloid leukemia: 9 chronic, 10 blastic, 2 with Ph1(22q-) translocation on 17 short arm. Ann. Gin&. 18, 239-240. Engel, E., B. J. McGee, B. J. Meyers, J. M. Flexner & S. B. Krantz (1977). Chromosome banding patterns of 49 cases of chronic myelocytic leukemia. N e w Engl. J . M e d . 296, 1295. Ford, J. H. & S. M. Pittman (1974). Duplication of 21 or 8/21 translocation in acute leukemia. Lancet ii, 1458. Ford, J. H., S. M. Pittman, S. Singh, E. J. Wass, P. C. Vincent & F. W. Gunz (1975). Cytogenetic basis of acute myeloid leukemia. J . nut. Cancer Inst. 55, 761-765. Fried, K., M. Rosenblatt & G. Mundel (1977). De novo balanced reciprocal translocation 46,XY,t(6;8)(913;q22). J . med. Genet. 14, 142-144. Fryns, V. P., H. Verresen & H. Van den Berghe (1974). Partial trisomy 8: Trisomy of the distal part of the long arm of chromosome number 8+(8q2) in a severely retarded and mallformed girl. Hum. Genet. 24, 241-246. Fujimoto, A., M. G. Wilson & J. W. Towner (1975). Familial inversion of chromosome no. 8. An affected child and a carrier fetus. Hum. Genet. 27, 67-73. Gafter, U., F. Shabtai, Y . Kahn, I. Halbrecht & M. Djaldetti (1976). Aplastic anemia followed by leukemia in congenital trisomy 8 mosaicism. Clin. Genet. 9, 134-142. Gahrton, G.,J. Lindsten & L. Zech (1974). Involvement of chromosomes 8, 9, 19 and 22 in Ph1 positive and Phi negative chronic myelocytic leukemia in the chronic or blastic stage. Acta med. scand. 196, 355-360. Gellis, A. S., M. Feingold, S. B. Cassidy, B. J. McGee & E. Engel (1975). Trisomy 8 syndrome. Anier. J . Dis. Child. 129, 951-952. Giovanella, B. C . , J. S. Stehlin, C. Santamaria, S. 0. Yim, A. C. Morgan, L. J. Williams, Jr., A. Leibovitz, P. J. Fialkow & D. M. Mumford (1976). Human neoplastic and normal cells in tissue culture. I-cell lines derived from malignant melanomas and normal melanocytes. J . nut. Cancer Inst. 56, 1131-1138. Guanti, G., G. Mollica, L. Polimeno & F. Maritato (1976). rDNA and acrocentric chromosomes in man. I. rDNA levels in a subject carrier of a 8p113p translocation and
323
in his unbalanced son, Hum. Genet. 33, 103-107. Gunz, F. W., B. I. Bach, P. E. Crossen, J. E. L. Mellor, S. Singh & P. C. Vincent (1973). Relevance of the cytogenetic status in acute leukemia in adults. J . nut. Cancer Inst. 50, 55-61. Hart, J. S., J. M. Trujillo, E. J . Freireich, S. L. George & E. Frei (1971). Cytogenetic studies and their clinical correlates in adults with acute leukemia. Ann. int. M e d . 75, 353-360. Hayata, I., M. Sakurai, S. Kakati & A. A. Sandberg (1975). Chromosomes and causation of human cancer and leukemia. XVI. Banding studies of chronic myelocytic leukemia, including five unusual Phl translocations. Cancer 36, 1177-1191. Hellstrom, K., L. Hagenfeldt, A. Larson, J. Lindsten, P. Sundelin & L. Tiepolo (1971). An extra C chromosome and various metabolic abnormalities in the bone marrow from a patient with refractory sideroblastic anemia. Scund. J . Haematol. 8, 923-930. Herva, R. & A. de la Chapelle (1976). A large pericentric inversion of human chromosome 8. Amer. J . hum. Genet. 28, 208212. Hook, E. B., N. H. Hatcher & 0. H. Calka (1975). Apparent “in situ” clone of cytogenetically marked ataxia-telangectasia lymphocytes. Hum. Genet. 30, 251-257. Hsu, L. Y. F., A. V. Alter & K. Hirschhorn (1974). Trisomy 8 in bone marrow of patients with polycythemia Vera and myelogenous leukemia. Clin. Genet. 6 , 258-264. Jonasson, J., G. Gahrton, J. Lindsten, C. Simonson-Lindemalm & L. Zech (1974). Trisomy 8 in acute myeloblastic leukemia and sideroachrestic anemia. Blood 43, 557-563. Kakati, S., M. Oshimura & A. A. Sandberg (1976). The chromosomes and causation of human cancer and leukemia, XIX. Common markers in various tumors. Cancer 38, 770777. Kawana, S., G. Watanabe, T. Asami, T. Okata & M. Yamamoto (1976). Pericentric inversion of chromosome No. 8. Tolioku J . exp. M e d . 119, 65-70. Kimberling, W. J., T. Fulbeck, L. Dixon & H. A. Lubs (1975). Localization of spherocytosis to chromosome 8 or 12 and report of a family with spherocytosis and a reciprocal translocation. A m e r . J . hum. Genet. 27, 586-594. Knudson, A. G., Jr., A. T. Meadows, W. W.
324
RlCCARDl AND FORGASON
Nichols & R. Hill (1976). Chromosomal deletion and retinoblastoma. N e w Engl. J . M e d . 295, 1120-1123. Kondo, I. (1976). Two cases of trisomy 8 mosaicism. f a p . J . hum. Genet. 21, 5-11. Koszyolanyi, G.,E. M. Buhler, P. Elmiger & G. R. Stalder (1976). Trisomy 8 mosaicism. Europ. J . Pediat. 123, 293-300. Ladda, R., L. Atkins, J. Littlefield, P. Neurath & K. M. Marimuthu (1974). Computer-assisted analysis of chromosomal abnormalities: Detection of a deletion in aniridiai Wilms’ tumor syndrome. Science 185, 784787. Lawler, S. D., D. S. Lobb & E. Wiltshaw (1975a). Philadelphia-chromosome positive bone marrow cells showing loss of the Y in males with chronic myeloid leukemia. Brit. J . Haemafol. 27, 247-252. Lawler, S. D., L. M. Secker-Walker, B. M. Summersgill, B. R. Reeves, J. Lewis, H. E. M. Kay & R. M. Hardisty (1975b). Chromosome banding studies in acute leukemia at diagnosis. Scand. J . Haernatol. 15, 312-320. Levan, G. & F. Mitelman (1975). Clustering of aberrations to specific chromosomes in human neoplasms. Hereditas (Lund) 79, 156-160. Lin, C. C., I. Uchida, M. Hotz, R. C. Miller, A. E. Greene & L. L. Coriell (1975). An (8;12) translocation, balanced, 46 chromosomes. Cytogenet. Cell Genet. 14, 78-79. Lindgren, V. & J. D. Rowley (1977). Comparable complex rearrangements involving 8:21 and 9;22 translocations in leukemia. Nature 266, 744-745. Linman, J. W. & G. C. Bagby (1976). The preleukemic syndrome: Clinical and laboratory features, natural course and management. Blood Cells 2, 11-31. Lundh, B., F. Mitelman, P. G. Nilsson, M. Stenstam & N. Soderstrom (1975). Chromosome abnormalities identified by banding technique in a patient with acute myeloid leukemia complicating Hodgkin’s disease. Scand. J . Haematol. 14, 303-307. Mark, J. (1973a). Origin of the ring chromosome in a human recurrent meningioma studied with G-band technique. Acta path. microbiol. scund. Sect. A 81, 588-590. Mark, J. (1973b). Karyotype patterns in human meningiomas. A comparison between studies with G- and Q-banding techniques. Hereditas (Lund) 75, 213-220. Mark, J., F. Mitelman & G. Levan (1972a). On the specificity of the G abnormality in
human meningiomas. Acta path. microbiol. scund. Sect. A 80, 812-820. Mark, J., F. Mitelman & G. Levan (1972b). Identification by fluorescence of the G chromosome lost in human meningiomas. Hereditas (Lund) 71, 163-168. McCaw, B. K., A. L. Epstein, H. S. Kaplan & F. Hecht (1977). Chromosome 14 translocations in African and North American Burkittt’s lymphoma. Znt. J . Cancer 19, 482-486. Mitelman, F. (1974). Heterogeneity o’f Phl in chronic myeloid leukemia. Hereditas (Lund) 76, 315-316. Mitelman, F. & G. Levan (1976). Clustering of aberrations t o specific chromosomes in human neuplasms. 11. A survey of 287 neoplasms. Hereditas (Lund) 82, 167-174. Mitelman, F., J. Mark, P. G. Nilsson, H. Dencker, C. Norryd & K. G. Tranberg (1974). Chromosome banding pattern in a human colonic polyps. Hereditas (Lund) 78, 63-68. Mitelman, F., P. G. Nilsson & L. Brandt (1975). Abnormal clones resembling those seen in blast crisis arising in the spleen in chronic myelocytic leukemia. J . nut. Cancer Znst. 54, 1319-1320. Mitelman, F., P. G. Nilsson, G. Levan & L. Brandt (1976). Non-random chromosome changes in acute myeloid leukemia. Chromosome banding examination of 30 cases at diagnosis. Int. J . Cancer 18, 31-38. Muller, H. & G. R. Stalder (1976). Chromosomes and human neoplasms. Achievements using new staining techniques. Europ. J . Pediat. 123, 1-13. Niebuhr, E. (1973). A familial translocation t(6q+ ;8q-) identified by fluorescence microscopy. Hum. Genet. 18, 189-192. Niss, R. & E. Passarge (1976). Trisomy 8 restricted t o cultered fibroblasts. J . m e d . Genet. 13, 229-234. Nowell, P. C. (1976). The clonal evolution of tumor cell populations. Science 194, 23-28. Nowell, P. C. & D. A. Hungerford (1960). A minute chromosome in human chronic granulocytic leukemia. Science 132, 197-198. Orye, E. & M. Craen (1976). A new chromosome deletion syndrome. Report of a patient with 46,XY,8p - chromosome constitution. Clin. Genet. 9, 289-301. Oshimura, M., I. Hayata, S. Kakati & A. A. Sandberg (1976). Chromosomes and causation of human cancer and leukemia. XVII.
CHROMOSOME 8 AND NEOPLASIA
Banding studies in acute myeloblastic Ieukemia (AML). Cancer 38, 748-761. Panani, A., A. G. Papayannis, K. Kyrkou & C. Gardikas (1977). Cytogenetic studies in preleukemia using the G-banding staining technique. Scand. J . Haemntol. 18, 301-308. Patil, S., B. K. McCaw, F. Hecht, D. Linder & E. Lovrien (1978). Human benign ovarian teratomas: chromosomal and electrophoretic enzyme studies. Birth Defects: Original Article Series, Vol. X l V , No. 6b, 297-301. Philip, P. (1975). Trisomy 8 in acute myeloid leukemia. Scand. J . Haematol. 14, 14@-147. Philip, P., G . L. Wantzin, M. K. Jensen & A. Drivsholm (1977). Trisomy 8 in acute myeloid leukemia: A non-random event. Scand. J . Haonatol. 18, 163-169. Prigogina, E. L. & E. W. Fleischman (1975). Certain patterns of karyotype evolution in chronic myelogeneous leukemia. Hum. Genet. 30, 113-119. Reiss, J. A,, P. Brenes, R. E. Magenis & J. Chamberlin (1977). The 8p - syndrome. (Abstract). 1977 Birth Defects Conference, Memphis, Tennessee, June 8-10. Rethore, M., A. Aurias, J. Couturier, B. Dutrillaux, M. Prieur & J. Lejuene (1977). Chromosome 8: Complete et Trisomies Segmentaires. Ann. Gknkt. 20, 5-11. Riccardi, V. M. (1977). Trisomy 8: An international study of 70 patients. Birth Defects: Original Article Series Vol. X l I l , No. 312, 171-184. Riccardi, V. M., J. Humbert & D. Peakman (1978a). Acute leukemia associated with trisomy 8 mosaicism and a familial translocation 46,XY,t(7;20)(~13;~12).Amer. J . med. Genet. 2, 15-21. Riccardi, V. M., E. Sujansky, A. C. Smith & U. Francke (1978b). Chromosomal imbalance in the aniridia-Wilms tumor association: l l p interstitial deletion. Pediatrics 61, 604-610. Rodewald, A., S. Stengel-Rutkowski, P. Schulz & H. Cleve (1977). Partial monosomy 8p. An attempt to establish a new chromosome deletion syndrome. Europ. J . Pediat. 125, 45-57. Rosenthal, I. M., E. Krrnpotic, M. Bocian & K. Szego (1973). Trisomy of the short arm of chromosome 8: Association with translocation between chromosomes 8 and 22, 46,XY,22 - ,t(8p;22q)+. Clin. Genet. 4, 507516. Rowley, J. D. (1973a). A new consistent chromosomal abnormality in chronic mye-
325
logenous leukemia identified by quinacrine fluorescence and Giemsa staining. Nature 243, 290-293. Rowley, J. D. (1973b). Identification of a translocation with quinacrine fluorescence in a patient with acute leukemia. Ann. Genet. 16, 109-112. Rowley, J. D. (1973~).Acquired trisomy 9. Lancet ii, 390. Rowley, J. D. (1974). Missing sex chromosomes and translocations in acute leukemia. Lancet ii, 835-836. Rowley, J. D. (1975a). Non-random chromosomal abnormalities in hematologic disorders of man. Proc. nut. Acad. Sci (Wash.) 72, 152-156. Rowley, J. D. (1975b). Abnormalities of chromosome 1 in myeloproliferative disorders. Cancer 36, 1748-1758. Rowley, J. D. (1977). Population cytogenetics of leukemia. Population Cytogenetics Studies in Humans, ed. Hook, E. B. & 1. H. Porter. New York, Academic Press Inc pp. 189-216. Rowley, I. D. & D. Potter (1976). Chromosomal banding patterns in acute non-lymphocytic leukemia. Blood 47, 705-721. Rowley, J. D. & A. A. Sandberg (1977). Personal communications corroborating and clarifying cited data. Sakurai, M. & A. A. Sandberg (1976). Chromosomes and causation of human cancer and leukemia. XI. Correlation of karyotypes with clinical features of acute myeloblastic leukemia. Cancer 37, 285-299. Sakurai, M., M. Oshimura, S. Kakati & A. A. Sandberg (1974). 8-21 translocation and missing sex chromosomes in acute leukemia. Lancet ii, 227-228. Sanchez, 0. & J. J. Yunis (1974). Partial trisomy 8 (8q24) and the trisomy-8 syndrome. Hum. Genet. 23, 297-303. Schinzel, A. (1977). Partial trisomy 8 in halfsisters with distinct dysmorphic patterns not similar to the trisomy 8 mosaicism syndrome. Hum. Genet. 37, 17-26. Sonta, S., M. Oshimura, J. T. Evans & A. A. Sandberg (1977). Chromosomes and causation of human cancer and leukemia. XX. Banding patterns of primary tumors. J . nut. Cancer Inst. 58, 49-53. Taillemete, J. L., J. Channarond, H. Tinel, W. Mulliez & C. Roux (1975). Deletion partielle du bras court du chromosome 8. Ann. Ge'nkt. 18, 251-255. Tiepolo, L. & 0. Zuffardi (1973). Identifica-
326
RlCCARDl AND FORGASON
tion of normal and abnormal chromosomes in tumor cells. Cytogenct. Cell Genet. 12, 8-16. Weinfeld, A., J. Westin & B. Swolin (1977). Ph1-negative eosinophilic leukemia with trisomy 8. Scand. J . Haematol. 18, 413-420. Weleber, R. G., R. S. Verma, W. J. Kimberling, H. G. Fieger, Jr. & H. A. Lubs (1976). Duplication-deficiency of the short arm of chromosome 8 following artificial insemination. Ann. Genet. 19, 241-247. Wurster-Hill, D. H. & D. Hoefnagel (1974). Banding identification of partial trisomy 15 of 8/21 translocation. J . ment. D e f . Res. 18, 139-144. Yamada, K. & S. Furusawa (1976). Preferential involvement of chromosomes no. 8 and no. 21 in acute leukemia and preleukemia. Blood 47, 679-686.
Yanagisawa, S. (1973). Partial trisomy 8: Further observation of a familial C/G translocation chromosome identified by the Qstaining methods. J . ment. Defic. Res. 17, 28-32. Zech, L., U. Haglund, K. Nilsson & G. Klein (1976). Characteristic chromosomal abnormalities in biopsies and lymphoid cell lines lfrom patients with Burkitt and nonBurkitt lymphomas. Int. J . Cancer 17, 47-56. Address: Vincent M . Riccardi, M . D . Klcberg Genetics Center Baylor College of Medicine Texas Medical Center Houston, Texas 77030 U .S . A .
