SHORT COMMUNICATION Trisomy 8 in Primary Esthesioneuroblastoma Donald R. VanDevanter, Diana George, Michael A. McNutt, Arthur Vogel, and Frederick Luthardt
ABSTRACT: Esthesianeuroblastama is a rare malignancy believed to be derived from neuroectodermal stem cells within the olfactory epithelium. We have obtained the karyotype of a primary esthesioneuroblastoma following brief (7-day) in vitro culture, and have determined that the only observable cytogenetic anomaly is the presence of an additional chromosome 8. Previously, the karyotypes of two cell lines established from metastatic esthesianeuroblastomas have been reported to contain the equivalent of three copies of chromosome 8, in addition to other chromosomal aberrations, including the reciprocal translocation, t(11 ;22 )(q2 4 ;q12 ). Examination of the cytogenetic literature suggests that an extra copy of chromosome 8 is a common occurrence in undifferentiated small round cell tumors frequently observed to carry the t(11 ;22l, including esthesioneuroblastoma, Ewing's sarcoma, peripheral neuroepithelioma, Askin's tumor, and rhabdomyosarcoma. These data, combined with our report of a small round cell tumor with the karyotype 47,XY, + 8, indicate that trisomy 8 may be a common phenomenon in these tumors, and may also provide some sort of selective advantage to these tumor types.
INTRODUCTION Esthesioneuroblastoma is an undifferentiated small blue cell tumor that originates in the neuroectodermal stem cells of the olfactory epithelium. To date, the only karyotypic data on this rare malignancy have been obtained from three separate cell lines established from metastatic lesions. Two of these three lines possessed the t(11;22)(q24;q12) translocation [1, 2] c o m m o n to other undifferentiated small blue cell tumors such as Ewing's sarcoma [3, 4], Askin's tumor [5, 6], and peripheral neuroepithelioma [7-9]. In addition, these two esthesioneuroblastoma cell lines possessed other chromosome aberrations, including the equivalent of an additional copy of chromosome 8 [1, 2]. We have performed cytogenetic studies on a short-term (7-day) culture of a primary esthesioneuroblastoma, and found trisomy 8 to be the only cytogenetic abnormality present. In reviewing the published karyotypes of undifferentiated small blue ceil tumor types that frequently possess the t(11;22)(q24;q12), the presence of an extra copy of chromosome 8 was not u n c o m m o n , suggesting a role for trisomy 8 in the development of these tumors.
From the ClinicalResearch Division(D. R. V.),TumorInstitute,Swedish Hospital MedicalCenter,Seattle; Laboratory of Pathology, Inc. (D. G., M. A. M., A. V.), Seattle; and Divisionof Perinatal Medicine(F. L.), Swedish llospital MedicalCenter, Seattle, Washington. Address reprint requests to: Donald R. VanDevanter, Tumor Institute, Swedish Hospital Medical Center, 409 Eklind Hall, 747 Summit Avenue, Seattle, W A 98104. Received March 18, 1991; accepted May 10, 1991.
133 © 1991 ElsevierSciencePublishingCo., Inc. 655 Avenueof the Americas,New York, NY 10010
Cancer Genet Cytogenet 57:133-136 (1991) 0165-4608/91/$03.50
134
D.R. VanDevanter
CASE REPORT AND CYTOGENETIC STUDY The patient was a 46-year-old Philippino male who presented with epistaxis in July of 1990. On examination, a tumor mass was found that extended from the superior nasal cavities into the orbit and through the cribriform plate. Initial evaluation revealed no evidence of metastases, and the tumor was resected. Portions of resected tumor were fixed in Carnoy's fixative for immunohistochemical analysis, and in formalin for routine histologic evaluation. There were diffuse small blue (:ell infiltrates in soft tissue and around bone with a relatively high incidence of mitoses and vascular invasion. Rosette formation of tumor cells was noted, as was the expression of some neural markers (chromogranin and synaptophysin) and low molecular weight keratin in a minority of cells. Expression of neurnfilament, neuron-specific enolase, and high molecular weight keratin was not observed. The histologic pattern of the neoplasm and the expression of neural antigens, together with the expression of cytokeratin in this clinical context, led to a diagnosis of esthesioneuroblastoma [10, 11]. An independent analysis performed by a second pathology group from a separate institution on previous biopsy tissue supported this diagnosis. A section of tumor tissue was mechanically minced to single cells and cultured in a 4 : 1 mixture of alpha MEM medium supplemented with 10% fetal bovine serum and Chang's medium [12]. The minced cells attached to flasks immediately and grew rapidly without apparent contact inhibition. By the first day after subculure (day 7), sufficient metaphases were obtained to perform trypsin-giemsa banding and karyotypic analysis. Of 27 G-banded metaphases examined, 25 displayed the identical karyotype of 47,XY, + 8 (Fig. 1). The remaining two metaphases were normal (46,XY), and are presumed to be derived from normal cells within the tumor tissue studied. DISCUSSION Esthesioneuroblastoma is a neoplasm of the nasal epithelium that typically occurs in individuals between 30 and 50 years of age. This tumor is extremely rare, with a total of 3 reported diagnoses in 1986 among the 25 million individuals followed by the Surveillance Epidemiology and End Results Program of the National Cancer Institute. The presence of neuroendocrine granules, as well as the variable expression of chromogranins, neurofilament proteins, and synaptophysin in esthesioneuroblastomas are consistent with the origin of this tumor in primitive cells derived from the neural crest [10, 11]. These properties are shared by some other undifferentiated small blue cell tumors, such as peripheral neuroepithelioma. Recent cell line evidence suggests that Ewing's sarcoma may also be derived from neural (:ells [13, 14]. This study contains the first report (to our knowledge) of the karyotype of a primary esthesioneuroblastoma obtained from short-term (7-day) culture. Previously, the karyotypes of three esthesioneuroblastoma cell lines established from metastatic lesions have been reported [1, 2]. Interestingly, two of these three established lines possessed the equivalent of an extra copy of chromosome 8, but also displayed the reciprocal t(11 ;22)(q24;q12) and other aberrations [1, 2]. While extremely rare in solid tumors, trisomy 8 as a lone chromosomal aberration is common in nonlymphocytic leukemias, the myeloproliferative disorders polycythemia vera and myelosclerosis, and the dysmyelopoietic syndromes preleukemia, sideroblastic anemia, pancytopenia, and aplastic anemia [15]. Recent evidence suggests strongly that the translocation t(11;22)(q24;q12), which was originally found in Ewing's sarcoma [3], is also a common feature of the peripheral neuroectodermal tumors. To date, seven of seven peripheral neuroepithelioma karyotypes reported have contained the t(11;22) [7-9[, as have three cases of Askin's tumor [5, 6] and two of three esthesioneuroblastoma cell lines [1, 2]. However, while the
135
Trisomy 8 in Esthesioneuroblastoma
,( 1
2
3
4
3-I-j-l-I-I 6
7
8
9
5
l-r 10
11
12
16
17
18
l(" Wf I¢ 13
14
-:~--~- -il-~ 19
20 Figure 1
15
,-i- -~-~2t
22
~ -r X
Y
G-banded karyotype (47,XY,+ 8} of a primary esthesioneuroblastoma metaphase.
t(11 ;22J has come to be considered diagnostic for peripheral neuroectodermal tumors [16], it is not present in all cases [6, 17]. In this study, we report a primary esthesioneuroblastoma karyotype of 47,XY, + 8 (Fig. 1). As noted above, two of three previous esthesioneuroblastoma karyotypes contained the equivalent of three copies of chromosome 8 in addition to the t(11;22) [1, 2], suggesting that an extra chromosome 8 may be a common occurrence in esthesioneuroblastoma. Because it has been noted that undifferentiated small blue cell tumors, including esthesioneuroblastoma, share a propensity for generation of the t(11;22} [1-9], we have surveyed the cytogenetic literature to determine whether trisomy 8 was also common among these tumor types. Whang-Peng and colleagues have noted that an additional chromosome 8 was the most common numerical abnormality in 22 patients with t(11;22) in small round cell tumors, including peripheral neuroectodermal tumors, Ewing's sarcomas, and rhabdomyosarcomas [6]. Four Ewing's sarcoma cell lines carrying the t(11;22) that also contain trisomy 8 or partial trisomies of the long arm of chromosome 8 have also been described [4]. Additional copies of chromosome 8 have also been observed in peripheral neuroectodermal tumors lacking the t(11;22) [17]. These observations suggest that the acquisition of an additional copy of chromosome 8 may indeed be a common phenomenon in undifferentiated small blue cell
136
D.R. VanDevanter tumors. W h i l e it r e m a i n s to be p r o v e n w h e t h e r an a d d i t i o n a l c h r o m o s o m e 8 p r o v i d e s s o m e sort of s e l e c t i v e a d v a n t a g e to these n e o p l a s m s , our report of a p r i m i t i v e b l u e cell t u m o r karyotype of 47,XY, + 8 w o u l d s u p p o r t s u c h a h y p o t h e s i s . The authors would like to thank Drs. Charles Caplan, James Huehnergarth, John Bolen, Steven (;lark, and Thomas Vaughn for informative discussions regarding this work. Supported in part by the Tumor Institute Cancer Research Fund.
REFERENCES 1. Whang-Peng J, Freter CE, Knutsen T, Nafro JJ, Gazdar A (1987): Translocation t(11;22] in esthesioneuroblastoma. Cancer Genet Cytogenet 29:155-157. 2. Cavazzana AO, Navarro S, Noguera R, Reynolds PC, Triche TJ (1988J: Olfactory neuroblastoma is not a neuroblastoma but is related to primitive neuroectodermal tumor (PNET). Advances in Neuroblastoma Research 2. Alan R. Liss, Inc., New York, pp. 463-473. 3. Aurias A, Rimbaut C, Buffe D, Dubousset J, Mazabraut A {1983]: Translncation of chromosome 22 in Ewing's sarcoma. N Engl J Med 309:496-497. 4. Turc-Carel Co Philip 1, Berger M, Philip T, Lenoir GM (1984): Chromosome study of Ewing's sarcoma (ES) cell lines. Consistency of a reciprocal translocation t(11:22)(q24;ql 2]. Cancer Genet Cytogenet 12:1-19. 5. de Chadaverian JP, Vekeman M, Seemayer TA (1984): Reciprocal translocation in small-cell sarcomas. N Engl I Med 311:1702-1703. 6. Whang-Peng J, Triche TI, Knutsen T, Miser 1, Kao-Shan S, Tsai S, Israel MA (1986): Cytogenetic characterization of selected small round cell tumors of childhood. Cancer Genet Cytogenet 21:185-208. 7. Lopez-Gines C, Pellin A, Llombart-Bosch A (1988): Two new cases of primary peripheral neuroepithelioma of soft tissue with translocation t(11 ;22)(q24;q121. Cancer Cenet Cytngenet 33:291-297. 8. Whang-Peng J, Triche TJ, Knutsen T, Miser J, Douglass EC, Israel MA (1984): Chromosome translocation in peripheral neuroepithelioma. N Engl I Med 311:584-585. 9. Miozzo M, Sozzi G, Calderone C, Pilotti S, Lombardi 1,, Pierotti MA, Della Porta G (1990: t(11;22) in three cases of peripheral neuroepithelioma. Genes Chrom Cancer 2:163-165. 10. Mills SE, ant] Frieson HF (1985}: Olfactory neuroblastoma. A clinicopathologic study of 21 cases. Am J Surg Pathol 9:317-327. 11. Taxy JB, Bharani NK, Mills SE, Frierson HF, Gould VE (1986}: The spectrum of olfactory neurotumors. A light-microscopic immunohistochemical and ultrastructural analysis. Am I Surg Pathol 10:687-695. 12. (;hang H-c, Jones OW, Masui H (1982}: Human amniotic fluid cells grown in hormonesupplemented medium: Suitability for prenatal diagnosis. Proc Natl Acad Sci USA 79:4795-4799. 13. Kawaguchi K, Koike M (1986): Neuron-specific enolase and leu-7 immunoreactive small round cell neoplasms. The relationship of Ewing's sarcoma in bone and soft tissue. Am 1 Pathol 86:79-83. 14. I,izard-Nacol S, Lizard G, lustrabo E, Turc-Carel C (1989): Immunologic characterization of Ewing's Sarcoma using mesenchymal and neural markers. Am l Pathol 135:847-856. 15. Mitelman F (1985): Human chromosome abnormalities--Catalogues and collections. Alan R. Liss, Inc., New York, Volume 5, pp. 203-248. 16. Fletcher JA, Kozakewich HP, Hoffer FA, Lage JM, Weidner N, Tepper R, Pinkus GS, Morton CC, Corson JM (1991}: Diagnostic relevance of clonal cytogenetic aberrations in malignant soft-tissue tumors. N Engl J Med 324:436-443. 17. Potluri VR, Gilbert F, Helsen C, Helson L (1987]: Primative neuroectodermal tumnr cell lines: chromosomal analysis of five cases. Cancer Genet Cytogenet 24:75-86.
ABSTRACT: Esthesianeuroblastama is a rare malignancy believed to be derived from neuroectodermal stem cells within the olfactory epithelium. We have obtained the karyotype of a primary esthesioneuroblastoma following brief (7-day) in vitro culture, and have determined that the only observable cytogenetic anomaly is the presence of an additional chromosome 8. Previously, the karyotypes of two cell lines established from metastatic esthesianeuroblastomas have been reported to contain the equivalent of three copies of chromosome 8, in addition to other chromosomal aberrations, including the reciprocal translocation, t(11 ;22 )(q2 4 ;q12 ). Examination of the cytogenetic literature suggests that an extra copy of chromosome 8 is a common occurrence in undifferentiated small round cell tumors frequently observed to carry the t(11 ;22l, including esthesioneuroblastoma, Ewing's sarcoma, peripheral neuroepithelioma, Askin's tumor, and rhabdomyosarcoma. These data, combined with our report of a small round cell tumor with the karyotype 47,XY, + 8, indicate that trisomy 8 may be a common phenomenon in these tumors, and may also provide some sort of selective advantage to these tumor types.
INTRODUCTION Esthesioneuroblastoma is an undifferentiated small blue cell tumor that originates in the neuroectodermal stem cells of the olfactory epithelium. To date, the only karyotypic data on this rare malignancy have been obtained from three separate cell lines established from metastatic lesions. Two of these three lines possessed the t(11;22)(q24;q12) translocation [1, 2] c o m m o n to other undifferentiated small blue cell tumors such as Ewing's sarcoma [3, 4], Askin's tumor [5, 6], and peripheral neuroepithelioma [7-9]. In addition, these two esthesioneuroblastoma cell lines possessed other chromosome aberrations, including the equivalent of an additional copy of chromosome 8 [1, 2]. We have performed cytogenetic studies on a short-term (7-day) culture of a primary esthesioneuroblastoma, and found trisomy 8 to be the only cytogenetic abnormality present. In reviewing the published karyotypes of undifferentiated small blue ceil tumor types that frequently possess the t(11;22)(q24;q12), the presence of an extra copy of chromosome 8 was not u n c o m m o n , suggesting a role for trisomy 8 in the development of these tumors.
From the ClinicalResearch Division(D. R. V.),TumorInstitute,Swedish Hospital MedicalCenter,Seattle; Laboratory of Pathology, Inc. (D. G., M. A. M., A. V.), Seattle; and Divisionof Perinatal Medicine(F. L.), Swedish llospital MedicalCenter, Seattle, Washington. Address reprint requests to: Donald R. VanDevanter, Tumor Institute, Swedish Hospital Medical Center, 409 Eklind Hall, 747 Summit Avenue, Seattle, W A 98104. Received March 18, 1991; accepted May 10, 1991.
133 © 1991 ElsevierSciencePublishingCo., Inc. 655 Avenueof the Americas,New York, NY 10010
Cancer Genet Cytogenet 57:133-136 (1991) 0165-4608/91/$03.50
134
D.R. VanDevanter
CASE REPORT AND CYTOGENETIC STUDY The patient was a 46-year-old Philippino male who presented with epistaxis in July of 1990. On examination, a tumor mass was found that extended from the superior nasal cavities into the orbit and through the cribriform plate. Initial evaluation revealed no evidence of metastases, and the tumor was resected. Portions of resected tumor were fixed in Carnoy's fixative for immunohistochemical analysis, and in formalin for routine histologic evaluation. There were diffuse small blue (:ell infiltrates in soft tissue and around bone with a relatively high incidence of mitoses and vascular invasion. Rosette formation of tumor cells was noted, as was the expression of some neural markers (chromogranin and synaptophysin) and low molecular weight keratin in a minority of cells. Expression of neurnfilament, neuron-specific enolase, and high molecular weight keratin was not observed. The histologic pattern of the neoplasm and the expression of neural antigens, together with the expression of cytokeratin in this clinical context, led to a diagnosis of esthesioneuroblastoma [10, 11]. An independent analysis performed by a second pathology group from a separate institution on previous biopsy tissue supported this diagnosis. A section of tumor tissue was mechanically minced to single cells and cultured in a 4 : 1 mixture of alpha MEM medium supplemented with 10% fetal bovine serum and Chang's medium [12]. The minced cells attached to flasks immediately and grew rapidly without apparent contact inhibition. By the first day after subculure (day 7), sufficient metaphases were obtained to perform trypsin-giemsa banding and karyotypic analysis. Of 27 G-banded metaphases examined, 25 displayed the identical karyotype of 47,XY, + 8 (Fig. 1). The remaining two metaphases were normal (46,XY), and are presumed to be derived from normal cells within the tumor tissue studied. DISCUSSION Esthesioneuroblastoma is a neoplasm of the nasal epithelium that typically occurs in individuals between 30 and 50 years of age. This tumor is extremely rare, with a total of 3 reported diagnoses in 1986 among the 25 million individuals followed by the Surveillance Epidemiology and End Results Program of the National Cancer Institute. The presence of neuroendocrine granules, as well as the variable expression of chromogranins, neurofilament proteins, and synaptophysin in esthesioneuroblastomas are consistent with the origin of this tumor in primitive cells derived from the neural crest [10, 11]. These properties are shared by some other undifferentiated small blue cell tumors, such as peripheral neuroepithelioma. Recent cell line evidence suggests that Ewing's sarcoma may also be derived from neural (:ells [13, 14]. This study contains the first report (to our knowledge) of the karyotype of a primary esthesioneuroblastoma obtained from short-term (7-day) culture. Previously, the karyotypes of three esthesioneuroblastoma cell lines established from metastatic lesions have been reported [1, 2]. Interestingly, two of these three established lines possessed the equivalent of an extra copy of chromosome 8, but also displayed the reciprocal t(11 ;22)(q24;q12) and other aberrations [1, 2]. While extremely rare in solid tumors, trisomy 8 as a lone chromosomal aberration is common in nonlymphocytic leukemias, the myeloproliferative disorders polycythemia vera and myelosclerosis, and the dysmyelopoietic syndromes preleukemia, sideroblastic anemia, pancytopenia, and aplastic anemia [15]. Recent evidence suggests strongly that the translocation t(11;22)(q24;q12), which was originally found in Ewing's sarcoma [3], is also a common feature of the peripheral neuroectodermal tumors. To date, seven of seven peripheral neuroepithelioma karyotypes reported have contained the t(11;22) [7-9[, as have three cases of Askin's tumor [5, 6] and two of three esthesioneuroblastoma cell lines [1, 2]. However, while the
135
Trisomy 8 in Esthesioneuroblastoma
,( 1
2
3
4
3-I-j-l-I-I 6
7
8
9
5
l-r 10
11
12
16
17
18
l(" Wf I¢ 13
14
-:~--~- -il-~ 19
20 Figure 1
15
,-i- -~-~2t
22
~ -r X
Y
G-banded karyotype (47,XY,+ 8} of a primary esthesioneuroblastoma metaphase.
t(11 ;22J has come to be considered diagnostic for peripheral neuroectodermal tumors [16], it is not present in all cases [6, 17]. In this study, we report a primary esthesioneuroblastoma karyotype of 47,XY, + 8 (Fig. 1). As noted above, two of three previous esthesioneuroblastoma karyotypes contained the equivalent of three copies of chromosome 8 in addition to the t(11;22) [1, 2], suggesting that an extra chromosome 8 may be a common occurrence in esthesioneuroblastoma. Because it has been noted that undifferentiated small blue cell tumors, including esthesioneuroblastoma, share a propensity for generation of the t(11;22} [1-9], we have surveyed the cytogenetic literature to determine whether trisomy 8 was also common among these tumor types. Whang-Peng and colleagues have noted that an additional chromosome 8 was the most common numerical abnormality in 22 patients with t(11;22) in small round cell tumors, including peripheral neuroectodermal tumors, Ewing's sarcomas, and rhabdomyosarcomas [6]. Four Ewing's sarcoma cell lines carrying the t(11;22) that also contain trisomy 8 or partial trisomies of the long arm of chromosome 8 have also been described [4]. Additional copies of chromosome 8 have also been observed in peripheral neuroectodermal tumors lacking the t(11;22) [17]. These observations suggest that the acquisition of an additional copy of chromosome 8 may indeed be a common phenomenon in undifferentiated small blue cell
136
D.R. VanDevanter tumors. W h i l e it r e m a i n s to be p r o v e n w h e t h e r an a d d i t i o n a l c h r o m o s o m e 8 p r o v i d e s s o m e sort of s e l e c t i v e a d v a n t a g e to these n e o p l a s m s , our report of a p r i m i t i v e b l u e cell t u m o r karyotype of 47,XY, + 8 w o u l d s u p p o r t s u c h a h y p o t h e s i s . The authors would like to thank Drs. Charles Caplan, James Huehnergarth, John Bolen, Steven (;lark, and Thomas Vaughn for informative discussions regarding this work. Supported in part by the Tumor Institute Cancer Research Fund.
REFERENCES 1. Whang-Peng J, Freter CE, Knutsen T, Nafro JJ, Gazdar A (1987): Translocation t(11;22] in esthesioneuroblastoma. Cancer Genet Cytogenet 29:155-157. 2. Cavazzana AO, Navarro S, Noguera R, Reynolds PC, Triche TJ (1988J: Olfactory neuroblastoma is not a neuroblastoma but is related to primitive neuroectodermal tumor (PNET). Advances in Neuroblastoma Research 2. Alan R. Liss, Inc., New York, pp. 463-473. 3. Aurias A, Rimbaut C, Buffe D, Dubousset J, Mazabraut A {1983]: Translncation of chromosome 22 in Ewing's sarcoma. N Engl J Med 309:496-497. 4. Turc-Carel Co Philip 1, Berger M, Philip T, Lenoir GM (1984): Chromosome study of Ewing's sarcoma (ES) cell lines. Consistency of a reciprocal translocation t(11:22)(q24;ql 2]. Cancer Genet Cytogenet 12:1-19. 5. de Chadaverian JP, Vekeman M, Seemayer TA (1984): Reciprocal translocation in small-cell sarcomas. N Engl I Med 311:1702-1703. 6. Whang-Peng J, Triche TI, Knutsen T, Miser 1, Kao-Shan S, Tsai S, Israel MA (1986): Cytogenetic characterization of selected small round cell tumors of childhood. Cancer Genet Cytogenet 21:185-208. 7. Lopez-Gines C, Pellin A, Llombart-Bosch A (1988): Two new cases of primary peripheral neuroepithelioma of soft tissue with translocation t(11 ;22)(q24;q121. Cancer Cenet Cytngenet 33:291-297. 8. Whang-Peng J, Triche TJ, Knutsen T, Miser J, Douglass EC, Israel MA (1984): Chromosome translocation in peripheral neuroepithelioma. N Engl I Med 311:584-585. 9. Miozzo M, Sozzi G, Calderone C, Pilotti S, Lombardi 1,, Pierotti MA, Della Porta G (1990: t(11;22) in three cases of peripheral neuroepithelioma. Genes Chrom Cancer 2:163-165. 10. Mills SE, ant] Frieson HF (1985}: Olfactory neuroblastoma. A clinicopathologic study of 21 cases. Am J Surg Pathol 9:317-327. 11. Taxy JB, Bharani NK, Mills SE, Frierson HF, Gould VE (1986}: The spectrum of olfactory neurotumors. A light-microscopic immunohistochemical and ultrastructural analysis. Am I Surg Pathol 10:687-695. 12. (;hang H-c, Jones OW, Masui H (1982}: Human amniotic fluid cells grown in hormonesupplemented medium: Suitability for prenatal diagnosis. Proc Natl Acad Sci USA 79:4795-4799. 13. Kawaguchi K, Koike M (1986): Neuron-specific enolase and leu-7 immunoreactive small round cell neoplasms. The relationship of Ewing's sarcoma in bone and soft tissue. Am 1 Pathol 86:79-83. 14. I,izard-Nacol S, Lizard G, lustrabo E, Turc-Carel C (1989): Immunologic characterization of Ewing's Sarcoma using mesenchymal and neural markers. Am l Pathol 135:847-856. 15. Mitelman F (1985): Human chromosome abnormalities--Catalogues and collections. Alan R. Liss, Inc., New York, Volume 5, pp. 203-248. 16. Fletcher JA, Kozakewich HP, Hoffer FA, Lage JM, Weidner N, Tepper R, Pinkus GS, Morton CC, Corson JM (1991}: Diagnostic relevance of clonal cytogenetic aberrations in malignant soft-tissue tumors. N Engl J Med 324:436-443. 17. Potluri VR, Gilbert F, Helsen C, Helson L (1987]: Primative neuroectodermal tumnr cell lines: chromosomal analysis of five cases. Cancer Genet Cytogenet 24:75-86.
