Complex Chromosome Rearrangements Involving 12q14 in Two Uterine Leiomyomas Nikos Pandis, Georgia Bardi, Kostas Sfikas, Nikos Panayotopoulos, Aliki Tserkezoglou, and Stelios Fotiou
ABSTRACT: Cytogenetic analysis of short-term cultures from 10 uterine leiomyomas revealed normal karyotypes in 8 and clonal complex chromosome rearrangements in 2 tumors. In both leiomyomas with clonal abnormalities, 12q14, but not 14q22-24, was involved in translocations with lq43 in one tumor and with 12q24 in the other. Additional chromosome abnormalities were found in both cases: 1-5 rings and monosomy of chromosome 9 in case 1, and complex numerical and structural abnormalities of chromosomes 1, 6-8, 11, 13, 16, 17, and 22 in case 2. The consistent cytogenetic rearrangement of 12q14 in uterine leiomyomas, sometimes without concomitant 14q changes, indicates that a gene of critical importance for leiomyoma development may be found in this band.
INTRODUCTION Recent cytogenetic studies of uterine leiomyomas have revealed that chromosomes 12 and 14 are rearranged in a substantial subgroup of tumors [1-9]. It has been suggested that secondary changes in uterine leiomyomas are also n o n r a n d o m [11]. We present the cytogenetic and histopathologic findings in 10 uterine leiomyomas. Two of the tumors showed clonal structural karyotypic abnormalities that involved 12q14 but not chromosome 14. MATERIALS AND METHODS Nine tumors were histologically diagnosed as typical uterine leiomyomas. One was an atypical or symplastic leiomyoma [11, 12]. Detailed information is presented later for the two cases with clonal chromosome aberrations. Case 1 The hysterectomy specimen from a 36-year-old w o m a n included a 5-cm tumor. Histologic examination revealed a submucosal tumor of moderately atypical smooth muscle fibers. Multinucleated cells, and cells with large hyperchromatic nuclei, were obFrom the Departmentof CellularPhysiology,"PapanikolaouResearch Center" (N. P., G. B.), Pathology (K. S.), and 1st Departmentof Gynecology(N. P., A. T., S. F.), HellenicAnticancerInstitute,Athens,Greece. Address reprint requests to: Dr. Nikos Pandis, Department of Cellular Physiology, "Papanikolaou Research Center," Hellenic Anticancer Institute, 171 Alexandras Ave., Athens 115 22, Greece. Received November 2, 1989; accepted January 25, 1990.
51 © 1990 ElsevierSciencePublishingCo., Inc. 655 Avenueof the Americas,New York, NY 10010
Cancer GenetCytogenet49:51-5G(1990) 0165-4608/90/$03.50
52
N. Pandis et al.
Figure 1
Histologic appearance of the atypical leiomyoma of case 1 (H&E, × 400).
served. Less than two mitotic figures per 10 high-power fields (HPF) were found. The diagnosis was atypical or symplastic leiomyoma (Fig. 1).
Case 2 The uterus from a 36-year-old w o m a n i n c l u d e d a 10-cm intramural tumor. Histologic e x a m i n a t i o n s h o w e d a typical smooth muscle tumor. The cells were arranged in bundles separated by masses of collagen. Elongated nuclei and moderate quantities of p r o t o p l a s m were observed (Fig. 2). T u m o r samples obtained i m m e d i a t e l y after surgery were m i n c e d with scissors and e n z y m a t i c a l l y disaggregated for 6 hours with 0.8% collagenase (510 U/mg, Sigma). Cultures were initiated in 25-cm 2 flasks, in RPMI 1640 m e d i u m s u p p l e m e n t e d with 17% fetal calf serum, glutamine, and antibiotics, and harvested after 5 - 6 days. Airdried c h r o m o s o m e preparations were made after hypotonic treatment with KC1 for 30 minutes followed by fixation in methanol/acetic acid (3:1). G-banding was ob-
Uterine Leiomyoma Cytogenetics
Figure 2
53
Histologic appearance of the typical leiomyoma of case 2 (H&E, x 100).
tained by Giemsa-trypsin or Wright stain. Karyotypes were constructed according to ISCN [13].
RESULTS
Eight cases had a normal female karyotype in all metaphases analyzed. Two tumors showed clonal karyotypic abnormalities.
Case 1
Nineteen metaphases could be analyzed in detail. All had t(1;12)(q43;q14), monosomy 9, and 1-5 ring chromosomes of unknown origin (Fig. 3). The chromosome number ranged from 46 to 50 depending on the number of rings.
54
N. Pandis et al.
3
2
6
7
8
4
9
10
5
11
i:' 13
14
12
X
:,i
15
16
17
18
OOOo 19
20
21
22
Y
Figure 3 Karyotype of case 1 showing t(1;12), monosomy 9, and 4 ring chromosomes. The deletion of the short arm of chromosome 5 was nonclonal. Breakpoints are indicated by arrows.
Case 2
Twenty-three metaphases were analyzed. All had 44 chromosomes with m o n o s o m y for c h r o m o s o m e s 8 and 22. Eight marker chromosomes were present in all metaphases. The interpretation of the karyotype (Fig. 4) was: 4 4 , X X , - 7 , - 8 , - 1 1 , - 22, inv(1)(q25q41),t(6;16)(p21;p 13),der(7)t(8;7)(7;11)(8pter--,8p12::7q35--~cen--~ 7p22::11q13--~l 1qter),der(11)t(8;11)(8qter--~8q12::11q13-->cen-->llpter), t(12;12)(q14;q24),dic(13;22)(p13;q12),t(6;16)(p21;p13),inv(17)(p12q21).
DISCUSSION Cytogenetic studies have demonstrated the presence of clonal abnormalities in uterine l e i o m y o m a s [1-9, 14]. The consistent finding of a t(12;14)(q14-15;q22-24), often as the sole anomaly, indicates that this is a primary change of importance in tumorigenesis. However, it is still unclear whether the critical gene is in a2q14-15 [7] or in 14q22-24 [5], or whether loci in both bands are essential and must be recombined if. a l e i o m y o m a is to develop. In the two cases with clonal abnormalities reported here, 12q14, but not 14q22-24, was involved. A translocation between 12q14 and lq43 was identified in case 1, and between 12q14 and q24 of the other chromosome 12 in case 2. Translocations of 12q14-15 with chromosomes other than 14 have previously been reported in only three uterine leiomyomas [2, 4, 6]: as t(X;12)(p22.3;q15), t(2;12)(q37;q14), and t(12;22), whereas only a single case with structural rearrangement of 14q22-24 but not of 12q has been reported [5]. The results presented here and those in the literature support the interpretation that rearrangements of 12q14-15 may be the key event in tumor development. However, the possibility remains that loci in 12q and 14q are equally important, and that in all cases mentioned above, the
Uterine Leiomyoma Cytogenetics
2
6
19
4
3
8
14
55
9
10
15
16
20
21
5
I1
17
X
lg
22
Y
Figure 4 Karyotype of case 2 stiowing t(12;12), monosomy of chromosomes 8 and 22, and structural rearrangements of chromosomes 1, 6-8, 11, 13, 16, 17, and 22 (see Results, for full karyotype interpretation). Breakpoints are indicated by arrows.
essential 12;14 recombination occurs, but sometimes involving only microscopically invisible chromosomal segments. This would be analogous to what is now known to occur in chronic myeloid leukemia with variant translocations [15]. The fact that 12q13-15 is rearranged also in several other types of benign and malignant tumors, in lipomas [16], pleomorphic adenomas of the salivary gland [17], and in myxoid liposarcomas [18] also points to the existence of a tumor-relevant gene in this region. Unless these changes represent "variant translocations," it is evident that a wide range of chromosomes can react with 12q13-15 with apparently identical tumorigenic effects. It is then tempting to speculate that the "least-common denominator" behind the various abnormalities may be the inactivation of a tumor suppressor gene in 12q13-15. The ring chromosomes and monosomy 9 in case I and the complex rearrangements of chromosomes 1, 6-8, 11, 13, and 17 in case 2 most likely represent secondary events. Ring chromosomes have also been reported by Nilbert et al. [10, 19] as secondary changes in both regular and bizarre uterine leiomyomas. In lipomas, they have been found as supernumerary chromosomes in an otherwise normal karyotype, and their presence has been associated with an atypical histology [16]. It is noteworthy that the diagnosis in case 1 was atypical leiomyoma. Therefore, we hypothesize that ring chromosomes may, as in lipomas, be a cytogenetic marker of atypia also in uterine leiomyomas.
The authors are grateful to Drs. Felix Mitelman and Sverre Heim (Department of Clinical Genetics, University Hospital, Lund, Sweden) for helpful comments.
56
N. P a n d i s et al.
REFERENCES 1. Heim S, Nilbert M, Vanni R, Flod6rus U-M, Mandahl N, Liedgren S, Lecca U, Mitelman F (1988): A specific translocation, t(12;14)(q14-15;q23-24), characterizes a subgroup of uterine leiomyomas. Cancer Genet Cytogenet 32:13-17. 2. Gibas Z, Griffin CA, Emanuel BS (1988): Clonal chromosome rearrangements in a uterine leiomyoma. Cancer Genet Cytogenet 32:19-24. 3. Turc-Carel C, Dal Cin P, Boghosian L, Terk-Zakarian J, Sandberg AA (1988): Consistent breakpoints in region 14q22-24 in uterine leiomyoma. Cancer Genet Cytogenet 32:25-31. 4. Vanni R, Lecca U (1988): Involvement of the long arm of chromosome 12 in chromosome rearrangements of uterine leiomyoma. Cancer Genet Cytogenet 32:33-34. 5. Mugneret F, Lizard-Nacol S, Volk C, Cuisenier J, Colin F, Turc-Carel C (1988): Association of breakpoint 14q23 with uterine leiomyoma. Cancer Genet Cytogenet 34:201-206. 6. Mark J, Havel G, Grepp C, Dahlenfors R, Wedell B (1988): Cytogenetical observations in human benign uterine leiomyomas. Anticancer Res 8:621-626. 7. Vanni R, Nieddu M, Paoli R, Lecca U (1989): Uterine leiomyoma cytogenetics. I. Rearrangements of chromosome 12. Cancer Genet Cytogenet 37:49-54. 8. Nilbert M, Heim S, Flod6rus U-M, Willen H, Mitelman F (1988): Karyotypic rearrangements in 20 uterine leiomyomas. Cytogenet Cell Genet 49:300-304. 9. Jani Sait SN, Dal Cin P, Ovanessoff S, Sandberg AA (1989): A uterine leiomyoma showing both t(12;14) and del(7) abnormalities. Cancer Genet Cytogenet 37:157-161. 10. Nilbert M, Heim S, Flod6rus U-M, Willen H, Akerman M, Mitelman F (1988): Ring formation and structural rearrangements of chromosome I as secondary changes in uterine leiomyomas with t(12;14)(q14-q15;q23-24). Cancer Genet Cytogenet 36:183-190. 11. Zaloudek C, Norris HJ (1987): Mesenchymal tumors of the uterus. In: Blaustein's Pathology of the Female Genital Tract, 3rd Ed., RJ Kurman, ed. Springer-Verlag, New York, pp. 373-408. 12. Hendrichson MR, Kempson RL (1989): The uterine corpus. In: Diagnostic Surgical Pathology, Vol. 2, Sternberg SS, ed. Raven Press, New York, pp. 1636-1646. 13. ISCN (1985): A International System for Cytogenetic Nomenclature, Harnden DG, Klinger (eds.); published in collaboration with Cytogenet Cell Genet (Karger, Basel, 1985); also in Birth Defects: Original Article Series, Vol. 21, No. 1 (March of Dimes Birth Defects Foundation, New York, 1985). 14. Boghosian L, Dal Cin P, Sandberg AA (1988): An interstitial deletion of chromosome 7 may characterize a subgroup of uterine leiomyoma. Cancer Genet Cytogenet 34:207-208. 15. Heim S, Billstr6m R, Kristoferson U, Mandahl N, Str6mbeck B, Mitelman F (1985): Variant Ph 1 translocations in chronic myeloid leukemia. Cancer Genet Cytogenet 18:215-227. 16. Mandahl N, Heim S, Arheden K, Rydholm A, Will6n H, Mitelman F (1988): Three major cytogenetic subgroups can be identified among chromosomally abnormal solitary lipomas. Hum Genet 79:203-208. 17. Bullerdiek J, Bartnitzke S, Weinberg M, Chilla R, Haubrich J, Schloot W (1987): Rearrangements of chromosome region 12q13-q15 in pleomorphic adenomas of human salivary gland (PSA). Cytogenet Cell Genet 45:187-190. 18. Turc-Carel C, Limon J, Dal Cin P, Karakousis C, Sandberg AA (1986): Cytogenetic studies of adipose tissue tumors. II. Recurrent reciprocal translocation t(12;16)(q13;p11) in myxoid liposarcomas. Cancer Genet Cytogenet 23:291-299. 19. Nilbert M, Heim S, Mandahl N, Flod6rus U-M, Will6n H, Baldetorp Bo, Mitelman F (1989): Complex karyotypic anomalies in a bizarre leiomyoma of the uterus. Genes Chrom Cancer 1:131-134.
ABSTRACT: Cytogenetic analysis of short-term cultures from 10 uterine leiomyomas revealed normal karyotypes in 8 and clonal complex chromosome rearrangements in 2 tumors. In both leiomyomas with clonal abnormalities, 12q14, but not 14q22-24, was involved in translocations with lq43 in one tumor and with 12q24 in the other. Additional chromosome abnormalities were found in both cases: 1-5 rings and monosomy of chromosome 9 in case 1, and complex numerical and structural abnormalities of chromosomes 1, 6-8, 11, 13, 16, 17, and 22 in case 2. The consistent cytogenetic rearrangement of 12q14 in uterine leiomyomas, sometimes without concomitant 14q changes, indicates that a gene of critical importance for leiomyoma development may be found in this band.
INTRODUCTION Recent cytogenetic studies of uterine leiomyomas have revealed that chromosomes 12 and 14 are rearranged in a substantial subgroup of tumors [1-9]. It has been suggested that secondary changes in uterine leiomyomas are also n o n r a n d o m [11]. We present the cytogenetic and histopathologic findings in 10 uterine leiomyomas. Two of the tumors showed clonal structural karyotypic abnormalities that involved 12q14 but not chromosome 14. MATERIALS AND METHODS Nine tumors were histologically diagnosed as typical uterine leiomyomas. One was an atypical or symplastic leiomyoma [11, 12]. Detailed information is presented later for the two cases with clonal chromosome aberrations. Case 1 The hysterectomy specimen from a 36-year-old w o m a n included a 5-cm tumor. Histologic examination revealed a submucosal tumor of moderately atypical smooth muscle fibers. Multinucleated cells, and cells with large hyperchromatic nuclei, were obFrom the Departmentof CellularPhysiology,"PapanikolaouResearch Center" (N. P., G. B.), Pathology (K. S.), and 1st Departmentof Gynecology(N. P., A. T., S. F.), HellenicAnticancerInstitute,Athens,Greece. Address reprint requests to: Dr. Nikos Pandis, Department of Cellular Physiology, "Papanikolaou Research Center," Hellenic Anticancer Institute, 171 Alexandras Ave., Athens 115 22, Greece. Received November 2, 1989; accepted January 25, 1990.
51 © 1990 ElsevierSciencePublishingCo., Inc. 655 Avenueof the Americas,New York, NY 10010
Cancer GenetCytogenet49:51-5G(1990) 0165-4608/90/$03.50
52
N. Pandis et al.
Figure 1
Histologic appearance of the atypical leiomyoma of case 1 (H&E, × 400).
served. Less than two mitotic figures per 10 high-power fields (HPF) were found. The diagnosis was atypical or symplastic leiomyoma (Fig. 1).
Case 2 The uterus from a 36-year-old w o m a n i n c l u d e d a 10-cm intramural tumor. Histologic e x a m i n a t i o n s h o w e d a typical smooth muscle tumor. The cells were arranged in bundles separated by masses of collagen. Elongated nuclei and moderate quantities of p r o t o p l a s m were observed (Fig. 2). T u m o r samples obtained i m m e d i a t e l y after surgery were m i n c e d with scissors and e n z y m a t i c a l l y disaggregated for 6 hours with 0.8% collagenase (510 U/mg, Sigma). Cultures were initiated in 25-cm 2 flasks, in RPMI 1640 m e d i u m s u p p l e m e n t e d with 17% fetal calf serum, glutamine, and antibiotics, and harvested after 5 - 6 days. Airdried c h r o m o s o m e preparations were made after hypotonic treatment with KC1 for 30 minutes followed by fixation in methanol/acetic acid (3:1). G-banding was ob-
Uterine Leiomyoma Cytogenetics
Figure 2
53
Histologic appearance of the typical leiomyoma of case 2 (H&E, x 100).
tained by Giemsa-trypsin or Wright stain. Karyotypes were constructed according to ISCN [13].
RESULTS
Eight cases had a normal female karyotype in all metaphases analyzed. Two tumors showed clonal karyotypic abnormalities.
Case 1
Nineteen metaphases could be analyzed in detail. All had t(1;12)(q43;q14), monosomy 9, and 1-5 ring chromosomes of unknown origin (Fig. 3). The chromosome number ranged from 46 to 50 depending on the number of rings.
54
N. Pandis et al.
3
2
6
7
8
4
9
10
5
11
i:' 13
14
12
X
:,i
15
16
17
18
OOOo 19
20
21
22
Y
Figure 3 Karyotype of case 1 showing t(1;12), monosomy 9, and 4 ring chromosomes. The deletion of the short arm of chromosome 5 was nonclonal. Breakpoints are indicated by arrows.
Case 2
Twenty-three metaphases were analyzed. All had 44 chromosomes with m o n o s o m y for c h r o m o s o m e s 8 and 22. Eight marker chromosomes were present in all metaphases. The interpretation of the karyotype (Fig. 4) was: 4 4 , X X , - 7 , - 8 , - 1 1 , - 22, inv(1)(q25q41),t(6;16)(p21;p 13),der(7)t(8;7)(7;11)(8pter--,8p12::7q35--~cen--~ 7p22::11q13--~l 1qter),der(11)t(8;11)(8qter--~8q12::11q13-->cen-->llpter), t(12;12)(q14;q24),dic(13;22)(p13;q12),t(6;16)(p21;p13),inv(17)(p12q21).
DISCUSSION Cytogenetic studies have demonstrated the presence of clonal abnormalities in uterine l e i o m y o m a s [1-9, 14]. The consistent finding of a t(12;14)(q14-15;q22-24), often as the sole anomaly, indicates that this is a primary change of importance in tumorigenesis. However, it is still unclear whether the critical gene is in a2q14-15 [7] or in 14q22-24 [5], or whether loci in both bands are essential and must be recombined if. a l e i o m y o m a is to develop. In the two cases with clonal abnormalities reported here, 12q14, but not 14q22-24, was involved. A translocation between 12q14 and lq43 was identified in case 1, and between 12q14 and q24 of the other chromosome 12 in case 2. Translocations of 12q14-15 with chromosomes other than 14 have previously been reported in only three uterine leiomyomas [2, 4, 6]: as t(X;12)(p22.3;q15), t(2;12)(q37;q14), and t(12;22), whereas only a single case with structural rearrangement of 14q22-24 but not of 12q has been reported [5]. The results presented here and those in the literature support the interpretation that rearrangements of 12q14-15 may be the key event in tumor development. However, the possibility remains that loci in 12q and 14q are equally important, and that in all cases mentioned above, the
Uterine Leiomyoma Cytogenetics
2
6
19
4
3
8
14
55
9
10
15
16
20
21
5
I1
17
X
lg
22
Y
Figure 4 Karyotype of case 2 stiowing t(12;12), monosomy of chromosomes 8 and 22, and structural rearrangements of chromosomes 1, 6-8, 11, 13, 16, 17, and 22 (see Results, for full karyotype interpretation). Breakpoints are indicated by arrows.
essential 12;14 recombination occurs, but sometimes involving only microscopically invisible chromosomal segments. This would be analogous to what is now known to occur in chronic myeloid leukemia with variant translocations [15]. The fact that 12q13-15 is rearranged also in several other types of benign and malignant tumors, in lipomas [16], pleomorphic adenomas of the salivary gland [17], and in myxoid liposarcomas [18] also points to the existence of a tumor-relevant gene in this region. Unless these changes represent "variant translocations," it is evident that a wide range of chromosomes can react with 12q13-15 with apparently identical tumorigenic effects. It is then tempting to speculate that the "least-common denominator" behind the various abnormalities may be the inactivation of a tumor suppressor gene in 12q13-15. The ring chromosomes and monosomy 9 in case I and the complex rearrangements of chromosomes 1, 6-8, 11, 13, and 17 in case 2 most likely represent secondary events. Ring chromosomes have also been reported by Nilbert et al. [10, 19] as secondary changes in both regular and bizarre uterine leiomyomas. In lipomas, they have been found as supernumerary chromosomes in an otherwise normal karyotype, and their presence has been associated with an atypical histology [16]. It is noteworthy that the diagnosis in case 1 was atypical leiomyoma. Therefore, we hypothesize that ring chromosomes may, as in lipomas, be a cytogenetic marker of atypia also in uterine leiomyomas.
The authors are grateful to Drs. Felix Mitelman and Sverre Heim (Department of Clinical Genetics, University Hospital, Lund, Sweden) for helpful comments.
56
N. P a n d i s et al.
REFERENCES 1. Heim S, Nilbert M, Vanni R, Flod6rus U-M, Mandahl N, Liedgren S, Lecca U, Mitelman F (1988): A specific translocation, t(12;14)(q14-15;q23-24), characterizes a subgroup of uterine leiomyomas. Cancer Genet Cytogenet 32:13-17. 2. Gibas Z, Griffin CA, Emanuel BS (1988): Clonal chromosome rearrangements in a uterine leiomyoma. Cancer Genet Cytogenet 32:19-24. 3. Turc-Carel C, Dal Cin P, Boghosian L, Terk-Zakarian J, Sandberg AA (1988): Consistent breakpoints in region 14q22-24 in uterine leiomyoma. Cancer Genet Cytogenet 32:25-31. 4. Vanni R, Lecca U (1988): Involvement of the long arm of chromosome 12 in chromosome rearrangements of uterine leiomyoma. Cancer Genet Cytogenet 32:33-34. 5. Mugneret F, Lizard-Nacol S, Volk C, Cuisenier J, Colin F, Turc-Carel C (1988): Association of breakpoint 14q23 with uterine leiomyoma. Cancer Genet Cytogenet 34:201-206. 6. Mark J, Havel G, Grepp C, Dahlenfors R, Wedell B (1988): Cytogenetical observations in human benign uterine leiomyomas. Anticancer Res 8:621-626. 7. Vanni R, Nieddu M, Paoli R, Lecca U (1989): Uterine leiomyoma cytogenetics. I. Rearrangements of chromosome 12. Cancer Genet Cytogenet 37:49-54. 8. Nilbert M, Heim S, Flod6rus U-M, Willen H, Mitelman F (1988): Karyotypic rearrangements in 20 uterine leiomyomas. Cytogenet Cell Genet 49:300-304. 9. Jani Sait SN, Dal Cin P, Ovanessoff S, Sandberg AA (1989): A uterine leiomyoma showing both t(12;14) and del(7) abnormalities. Cancer Genet Cytogenet 37:157-161. 10. Nilbert M, Heim S, Flod6rus U-M, Willen H, Akerman M, Mitelman F (1988): Ring formation and structural rearrangements of chromosome I as secondary changes in uterine leiomyomas with t(12;14)(q14-q15;q23-24). Cancer Genet Cytogenet 36:183-190. 11. Zaloudek C, Norris HJ (1987): Mesenchymal tumors of the uterus. In: Blaustein's Pathology of the Female Genital Tract, 3rd Ed., RJ Kurman, ed. Springer-Verlag, New York, pp. 373-408. 12. Hendrichson MR, Kempson RL (1989): The uterine corpus. In: Diagnostic Surgical Pathology, Vol. 2, Sternberg SS, ed. Raven Press, New York, pp. 1636-1646. 13. ISCN (1985): A International System for Cytogenetic Nomenclature, Harnden DG, Klinger (eds.); published in collaboration with Cytogenet Cell Genet (Karger, Basel, 1985); also in Birth Defects: Original Article Series, Vol. 21, No. 1 (March of Dimes Birth Defects Foundation, New York, 1985). 14. Boghosian L, Dal Cin P, Sandberg AA (1988): An interstitial deletion of chromosome 7 may characterize a subgroup of uterine leiomyoma. Cancer Genet Cytogenet 34:207-208. 15. Heim S, Billstr6m R, Kristoferson U, Mandahl N, Str6mbeck B, Mitelman F (1985): Variant Ph 1 translocations in chronic myeloid leukemia. Cancer Genet Cytogenet 18:215-227. 16. Mandahl N, Heim S, Arheden K, Rydholm A, Will6n H, Mitelman F (1988): Three major cytogenetic subgroups can be identified among chromosomally abnormal solitary lipomas. Hum Genet 79:203-208. 17. Bullerdiek J, Bartnitzke S, Weinberg M, Chilla R, Haubrich J, Schloot W (1987): Rearrangements of chromosome region 12q13-q15 in pleomorphic adenomas of human salivary gland (PSA). Cytogenet Cell Genet 45:187-190. 18. Turc-Carel C, Limon J, Dal Cin P, Karakousis C, Sandberg AA (1986): Cytogenetic studies of adipose tissue tumors. II. Recurrent reciprocal translocation t(12;16)(q13;p11) in myxoid liposarcomas. Cancer Genet Cytogenet 23:291-299. 19. Nilbert M, Heim S, Mandahl N, Flod6rus U-M, Will6n H, Baldetorp Bo, Mitelman F (1989): Complex karyotypic anomalies in a bizarre leiomyoma of the uterus. Genes Chrom Cancer 1:131-134.
