Multiple and Complex Abnormalities in a Case of Alveolar Soft-Part Sarcoma Chandrika Sreekantaiah, Frederick P. Li, Noel Weidner, and Avery A. Sandberg
ABSTRACT: Chromosomal analysis of two pulmonary metastases from a 25-year-old male with alveolar soft-part sarcoma of the right lower extremity revealed multiple and complex chromosomal abnormalities. The rearrangements included deletions and translocations affecting chromosomes 1, 2, 3.10, 11, 14, 15, and 16. Trisomy of chromosome 12 and loss of chromosome 17 was also observed.
INTRODUCTION A l v e o l a r s o f t - p a r t s a r c o m a is a c l i n i c a l l y a n d m o r p h o l o g i c a l l y d i s t i n c t s o f t - t i s s u e s a r c o m a . It is a n u n c o m m o n n e o p l a s m w i t h a n e s t i m a t e d f r e q u e n c y b e t w e e n 0.4% a n d 1.0% of all s o f t - t i s s u e s a r c o m a s . A l v e o l a r s o f t - p a r t s a r c o m a s are u n i f o r m l y m a l i g nant and have no benign counterparts. The tumor occurs principally in adolescents a n d y o u n g a d u l t s b e t w e e n 15 a n d 35 y e a r s of age. In a d u l t s t h e l o c a t i o n is m a i n l y i n t h e l o w e r e x t r e m i t i e s a n d i n c h i l d r e n it is o f t e n i n t h e h e a d a n d n e c k r e g i o n . T h e t u m o r u s u a l l y p r e s e n t s as a s l o w - g r o w i n g p a i n l e s s m a s s n e a r l y a l w a y s w i t h o u t f u n c t i o n a l i m p a i r m e n t . P r o g n o s i s is p o o r d e s p i t e t h e r e l a t i v e l y s l o w g r o w t h of t h e t u m o r a n d i n m o s t i n s t a n c e s m e t a s t a s i s o c c u r s e a r l y i n t h e c o u r s e of t h e d i s e a s e . T h e r e is c o n s i d e r able u n c e r t a i n t y as to its e x a c t h i s t o g e n e s i s [1]. We report the karyotypic findings in multiple metastatic pulmonary nodules from a p a t i e n t w i t h a l v e o l a r soft p a r t s a r c o m a of t h e r i g h t leg. T w o t u m o r s w e r e c h a r a c t e r i z e d b y e x t e n s i v e c l o n a l r e a r r a n g e m e n t s , n o g r o w t h w a s o b t a i n e d in one, a n d a n o r m a l karyotype was present in the other three.
CASE HISTORY T h e p a t i e n t is a 2 5 - y e a r - o l d m a l e w h o p r e s e n t e d in A u g u s t 1986 w i t h a m a s s in t h e r i g h t l o w e r e x t r e m i t y . In N o v e m b e r 1986 t h e p a t i e n t u n d e r w e n t a r i g h t a b o v e - t h e k n e e a m p u t a t i o n a n d a r i g h t t h o r a c o t o m y i n M a r c h 1987 for r e m o v a l of m e t a s t a t i c
From The Cancer Center of Southwest Biomedical Research Institute and Genetrix, Inc. (C. S.. A. A. S.), Scottsdale, Arizona; Clinical Studies Section, Clinical Epidemiology Branch, NCI (F. P. L.) Boston; and Department of Pathology, Brigham & Women's tlospital and flarvard Medical School (N. W.) Boston, Massachusetts. Address reprint requests to: Dr. Avery A. Sandberg, The Cancer Center of Southwest Biomedical Research Institute and Genetrix, Inc., 6401 E. Thomas Road. Scottsdale. A Z 85251. Received January 16, 1991; accepted February 22, 1991.
167 G 1991 Elsevier Science Publishing Co.. Inc. 655 Avenue of the Americas, New York. NY 10010
Cancer Genet Cytogenet 55:167 171 (1991) 0165-4608/91/$03.50
168
C. Sreekantaiah et al.
Figure 1 (A) Shown is the nestlike arrangement (alveolar pattern) of tumor cells typical of alveolar soft-part sarcoma. The nests, separated by sinusoidal vascular spaces, are made of large, atypical cells with abundant cytoplasm. They are poorly cohesive (PAS stain, original magnification × 40). (B) PAS stain shows tumor cells containing intracellular crystalline structures that are resistant to diastase digestion (arrowhead) [PAS stain, original magnification × 250).
nodules. The patient received c h e m o t h e r a p y {Adriamycin, DTIC, and ifosfamide) in May 1987. In A p r i l 1989 m u l t i p l e n o d u l e s in all lobes of the lung were seen again by c o m p u t e r i z e d tomography. A m e d i a s t i n o t o m y for p u l m o n a r y nodule resection was performed; a portion of each of six of these nodules were submitted for cytogenetic analyses. Histopathologic examination of m u l t i p l e nodules from the left and right u p p e r and lower lobes of the lung revealed metastatic alveolar soft part sarcoma (Fig. 1). I m m u n o p e r o x i d a s e studies and electron microscopic studies were consistent with the above diagnosis. A single metastases to the brain was treated with radiation in March 1989. F o l l o w i n g surgical removal of the m u l t i p l e metastatic p u l m o n a r y nodules, additional p u l m o n a r y metastases were noted by CT-scan, as well as several new brain metastases leading to paraplegia (at T10 level). This patient has been treated with trimetrexate.
MATERIALS A N D METHODS
The six tumor nodules received were processed according to a p r e v i o u s l y described procedure [2]. Harvest was i n d i v i d u a l i z e d for each flask and coverslip, the metaphases G-banded [3], and the karyotypes expressed according to the International System for Cytogenetic Nomenclature [4].
169
Chromosome Abnormalities in Alveolar Soft-Part Sarcoma
.
.
_
_
-
-
. . . . .
. .
.
.
.
.
1
2
3
6
7
El
1,3
14
15
-
-
19
. . . . . . . . . .
9
4
5
10
11
12
16
t7
1~
21
22
- - - I
20
Figure 2 G-bandedrepresentative karyotype (specimen No. 1) showing multiple and complex abnormalities (arrowhoads).
RESULTS
Six metastatic pulmonary nodules were received for cytogenetic analysis. Two of the tumors were from the right lower lobe, one from the right upper lobe, two from the left lower lobe and one from the left upper lobe. The karyotypic findings in each of the 6 nodules are given in Table 1 and representative abnormal karyotypes from specimens 1 and 2 are shown in Figures 2 and 3. Both these specimens had similar abnormalities except for a translocation involving chromosomes 1 and 16 that was present in specimen 1 only (Fig. 2). In addition, specimens 3-5 (from the right lower lobe and nodules from the left and right lower lobes, respectively) had apparently normal karyotypes. Considering the short culture time (usually 3-5 days) it is possible that the normal karyotypes from specimens 3-5 represent tumor cells, although overgrowth by fibroblasts cannot be ruled out. Specimen 6 from the left lower lobe failed to attach and grow in culture.
DISCUSSION
Cytogenetic analysis of this rare tumor has not been described earlier. The chromosomal abnormalities observed were multiple and complex. In the absence of cytogenetic data from the primary tumor it cannot be determined whether the chromosomal changes observed in the pulmonary nodules 1 and 2 represent the original karyotype. It is more probable that the complexity of the karyotype reflects tumor progression and appearance of secondary changes. These two tumors demonstrated similar karyotypic abnormalities, the difference being that the former specimen contained a der(16) chromosome not observed in the latter. It would appear that evolution of the clone had occurred in specimen 2.
170
c. Sreekantaiah et al.
1
2
8
_L__
~i i 6
_
4
5
11
12
17
18
.
~ 7
8
10
--'!:~'---
t3 ........
14 tw'__
19
20
15 ~ -I
16 ~'~r
F-'-'J, ........
21
'---'~--
22
8 -j
V
Figure 3 G-banded representative karyotype of specimen No. 2 with abnormalities similar to specimen 1. Both chromosomes 16 in this tumor are normal. Translocations and terminal deletions were the most c o m m o n rearrangements although trisomy 12 and m o n o s o m y 17 were also present. Two p u l m o n a r y nodules (specimens 1 and 2 in Table 1) showed clonal abnormalities involving chromosome 3 at band p21. N o n r a n d o m i n v o l v e m e n t of this band is c o m m o n in small cell lung cancers [5] and mesotheliomas [6] and has led to the suggestion that it may be the site of the primary genetic change. Deletions of the short arm of chromosome 3 around band p21 have also been observed in renal cell carcinomas [8] and ovarian and breast cancers [9]. Abnormalities of 3p may therefore be associated with a n u m b e r of different tumorigenic events. Oncogenes SKI, ARG, and TRK have been mapped to the long arm of chromosome 1, NMYC and REL to the short arm of chromosome 2, HRAS1, and ST2, the tumor suppressor gene to 11p, HST, INT2, SEA, BCL1 and ETS1 to 11q, KRAS2, [NT1, and GLI to chromosome 12, FES to 15q, ERBA1, ERBB2, and NEU, and growth factors CSF3 and NGFR to 17q [7], the other chromosomes involved in rearrangements in this study. A n u m b e r of mechanisms, such as (1) activation and/ or overexpression of the genes at the chromosomal breakpoints, (2) loss of tumor suppressor genes through deletion of chromosomes, or (3) amplification of genes on chromosome 12 and 3p, the regions present in extra copy, may therefore have contributed to the progression of the tumor. Although the growth of alveolar sarcoma is relatively slow, the ultimate prognosis is k n o w n to be poor. A 5-year survival rate of 60%, a lO-year survial rate of 38%, and a 20-year survival rate of 15% have been reported for patients who present without metastases [10]. In most instances metastasis occurs early in the course of the disease. The patient in our study u n d e r w e n t resection of the primary tumor in November 1986, and by April 1989 had metastatic sarcoma to the lungs and brain. It is possible that the cytogenetic picture reflects the aggressive nature of the neoplasm; the role played by the chemotherapy given in 1987 is difficult to evaluate.
171
C h r o m o s o m e A b n o r m a l i t i e s i n A l v e o l a r Soft-Part S a r c o m a
Table 1
C y t o g e n e t i c f i n d i n g s i n t h e six m e t a s t a t i c p u l m o n a r y n o d u l e s
Specimen number
Tumor site
Culture time (days)
1.
Right lower lobe #1
4-5
2.
Right upper lobe # 2
4-5
3,
Right lower lobe #3
5-6
4. 5. 6,
Left lower lobe #1 Left upper lobe #2 Left lower lobe # 3
20 5
Karyotype 5: 46,XY 10: 47,XY,- 1, + der(1)t(3;1)(1;?)(3pter--, p21::1p36.1--~cen--~q32::?),del(2)(p12), del(10)(p11.2),del(11)(q14), + der(11), t ( l l ;?)(p11.2;?), + 1 2 , - 14, + der(14)t(14:?) (pl 1;?),- 15, + der(15)t(?;15)(15;2)(?::15p11-~ cen--~q25::2p 12--~2pter), 16, + der(16)t(1:16) (q12;q24),- 17 12: 46,XY 1: 45,X, Y 3: 47,XY, 1,+der(1)t(3;1)(1;?)(3pter~ p21::lp36.1---,cen---,q32::?),del(2)(p12), del(10)(pl 1.21.del(11)(q14), + der(11)t(31:?) (p11.2;?),+ 12, 14, + der(14)t(14;?) (p11;?), - 15, + der(15)t(?:15)(15;2)(?::15p11---~ cen--~q25::2p12----~2pter), - 17 16: 46,XY 1: 46,XY,t(16;21)(p11;q11) 20: 46,XY 15: 46,XY No growth
The authors thank Robert Roeder and Fred Flohrschutz for help with the illustrations and Shirley Frazzini for secretarial assistance. The work was supported in part by Contract No. N01-CP71018 from the National Cancer Institute.
REFERENCES 1. Enzinger FM, Weiss SW (1988): Soft tissue tumors, second edition, The C.V. Mosby Company, Missouri. 2. Sreekantaiah C, Berger CS, Karakousis CP, Rao U, Leong SPL, Sandberg AA (1989): Cytogenetic subtype involving chromosome 13 in lipoma: Report of 3 cases. Cancer Genet Cytogenet 39:281-288. 3. Seabright M (1971): Rapid banding technique for h u m a n chromosomes. Lancet 2:971-972. 4. ISCN (1985): An International System for Human Cytogenetic Nomenclature Harnden DG, Klinger HP, 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). 5. Whang-Peng J, Koa-Shan CS, Lee EC, Bunn PA, Carney DN, Gazdar AF, Minna JD (1982): Specific chromosome defect associated with h u m a n small cell lung cancer: Deletion 3p(14-23). Science 215:181-182. 6. Hagemeijer A, Versnel MA, Van Drunen E, Moret M, Bouts MJ, van der Kwast Th. H, Hoogsteden HC (1990): Cytogenetic analysis of malignant mesothelioma. Cancer Genet Cytogenet 47:1-28. 7. Human Gene Mapping 10 (1989): Tenth International Workshop on Human Gene Mapping. Cytogenet Cell Genet 51:1-1148. 8. Walter TA, Berger CS, Sandberg AA (1989): The cytogenetics of renal tumors. Where do we stand, where do we go? Cancer Genet Cytogenet 43:15-34. 9. Sandberg AA (1990): The Chromosomes in Human Cancer and Leukemia, 2nd Edition Elsevier North-Holland, New York. 10. Lieberman PH, Brennan MF, Kimmel M, Erlandson RA, Garin-Chesa P, Flehinger BY (1989): Alveolar soft part sarcoma. A clinico-pathologic study of half a century. Cancer 63:1-13.
ABSTRACT: Chromosomal analysis of two pulmonary metastases from a 25-year-old male with alveolar soft-part sarcoma of the right lower extremity revealed multiple and complex chromosomal abnormalities. The rearrangements included deletions and translocations affecting chromosomes 1, 2, 3.10, 11, 14, 15, and 16. Trisomy of chromosome 12 and loss of chromosome 17 was also observed.
INTRODUCTION A l v e o l a r s o f t - p a r t s a r c o m a is a c l i n i c a l l y a n d m o r p h o l o g i c a l l y d i s t i n c t s o f t - t i s s u e s a r c o m a . It is a n u n c o m m o n n e o p l a s m w i t h a n e s t i m a t e d f r e q u e n c y b e t w e e n 0.4% a n d 1.0% of all s o f t - t i s s u e s a r c o m a s . A l v e o l a r s o f t - p a r t s a r c o m a s are u n i f o r m l y m a l i g nant and have no benign counterparts. The tumor occurs principally in adolescents a n d y o u n g a d u l t s b e t w e e n 15 a n d 35 y e a r s of age. In a d u l t s t h e l o c a t i o n is m a i n l y i n t h e l o w e r e x t r e m i t i e s a n d i n c h i l d r e n it is o f t e n i n t h e h e a d a n d n e c k r e g i o n . T h e t u m o r u s u a l l y p r e s e n t s as a s l o w - g r o w i n g p a i n l e s s m a s s n e a r l y a l w a y s w i t h o u t f u n c t i o n a l i m p a i r m e n t . P r o g n o s i s is p o o r d e s p i t e t h e r e l a t i v e l y s l o w g r o w t h of t h e t u m o r a n d i n m o s t i n s t a n c e s m e t a s t a s i s o c c u r s e a r l y i n t h e c o u r s e of t h e d i s e a s e . T h e r e is c o n s i d e r able u n c e r t a i n t y as to its e x a c t h i s t o g e n e s i s [1]. We report the karyotypic findings in multiple metastatic pulmonary nodules from a p a t i e n t w i t h a l v e o l a r soft p a r t s a r c o m a of t h e r i g h t leg. T w o t u m o r s w e r e c h a r a c t e r i z e d b y e x t e n s i v e c l o n a l r e a r r a n g e m e n t s , n o g r o w t h w a s o b t a i n e d in one, a n d a n o r m a l karyotype was present in the other three.
CASE HISTORY T h e p a t i e n t is a 2 5 - y e a r - o l d m a l e w h o p r e s e n t e d in A u g u s t 1986 w i t h a m a s s in t h e r i g h t l o w e r e x t r e m i t y . In N o v e m b e r 1986 t h e p a t i e n t u n d e r w e n t a r i g h t a b o v e - t h e k n e e a m p u t a t i o n a n d a r i g h t t h o r a c o t o m y i n M a r c h 1987 for r e m o v a l of m e t a s t a t i c
From The Cancer Center of Southwest Biomedical Research Institute and Genetrix, Inc. (C. S.. A. A. S.), Scottsdale, Arizona; Clinical Studies Section, Clinical Epidemiology Branch, NCI (F. P. L.) Boston; and Department of Pathology, Brigham & Women's tlospital and flarvard Medical School (N. W.) Boston, Massachusetts. Address reprint requests to: Dr. Avery A. Sandberg, The Cancer Center of Southwest Biomedical Research Institute and Genetrix, Inc., 6401 E. Thomas Road. Scottsdale. A Z 85251. Received January 16, 1991; accepted February 22, 1991.
167 G 1991 Elsevier Science Publishing Co.. Inc. 655 Avenue of the Americas, New York. NY 10010
Cancer Genet Cytogenet 55:167 171 (1991) 0165-4608/91/$03.50
168
C. Sreekantaiah et al.
Figure 1 (A) Shown is the nestlike arrangement (alveolar pattern) of tumor cells typical of alveolar soft-part sarcoma. The nests, separated by sinusoidal vascular spaces, are made of large, atypical cells with abundant cytoplasm. They are poorly cohesive (PAS stain, original magnification × 40). (B) PAS stain shows tumor cells containing intracellular crystalline structures that are resistant to diastase digestion (arrowhead) [PAS stain, original magnification × 250).
nodules. The patient received c h e m o t h e r a p y {Adriamycin, DTIC, and ifosfamide) in May 1987. In A p r i l 1989 m u l t i p l e n o d u l e s in all lobes of the lung were seen again by c o m p u t e r i z e d tomography. A m e d i a s t i n o t o m y for p u l m o n a r y nodule resection was performed; a portion of each of six of these nodules were submitted for cytogenetic analyses. Histopathologic examination of m u l t i p l e nodules from the left and right u p p e r and lower lobes of the lung revealed metastatic alveolar soft part sarcoma (Fig. 1). I m m u n o p e r o x i d a s e studies and electron microscopic studies were consistent with the above diagnosis. A single metastases to the brain was treated with radiation in March 1989. F o l l o w i n g surgical removal of the m u l t i p l e metastatic p u l m o n a r y nodules, additional p u l m o n a r y metastases were noted by CT-scan, as well as several new brain metastases leading to paraplegia (at T10 level). This patient has been treated with trimetrexate.
MATERIALS A N D METHODS
The six tumor nodules received were processed according to a p r e v i o u s l y described procedure [2]. Harvest was i n d i v i d u a l i z e d for each flask and coverslip, the metaphases G-banded [3], and the karyotypes expressed according to the International System for Cytogenetic Nomenclature [4].
169
Chromosome Abnormalities in Alveolar Soft-Part Sarcoma
.
.
_
_
-
-
. . . . .
. .
.
.
.
.
1
2
3
6
7
El
1,3
14
15
-
-
19
. . . . . . . . . .
9
4
5
10
11
12
16
t7
1~
21
22
- - - I
20
Figure 2 G-bandedrepresentative karyotype (specimen No. 1) showing multiple and complex abnormalities (arrowhoads).
RESULTS
Six metastatic pulmonary nodules were received for cytogenetic analysis. Two of the tumors were from the right lower lobe, one from the right upper lobe, two from the left lower lobe and one from the left upper lobe. The karyotypic findings in each of the 6 nodules are given in Table 1 and representative abnormal karyotypes from specimens 1 and 2 are shown in Figures 2 and 3. Both these specimens had similar abnormalities except for a translocation involving chromosomes 1 and 16 that was present in specimen 1 only (Fig. 2). In addition, specimens 3-5 (from the right lower lobe and nodules from the left and right lower lobes, respectively) had apparently normal karyotypes. Considering the short culture time (usually 3-5 days) it is possible that the normal karyotypes from specimens 3-5 represent tumor cells, although overgrowth by fibroblasts cannot be ruled out. Specimen 6 from the left lower lobe failed to attach and grow in culture.
DISCUSSION
Cytogenetic analysis of this rare tumor has not been described earlier. The chromosomal abnormalities observed were multiple and complex. In the absence of cytogenetic data from the primary tumor it cannot be determined whether the chromosomal changes observed in the pulmonary nodules 1 and 2 represent the original karyotype. It is more probable that the complexity of the karyotype reflects tumor progression and appearance of secondary changes. These two tumors demonstrated similar karyotypic abnormalities, the difference being that the former specimen contained a der(16) chromosome not observed in the latter. It would appear that evolution of the clone had occurred in specimen 2.
170
c. Sreekantaiah et al.
1
2
8
_L__
~i i 6
_
4
5
11
12
17
18
.
~ 7
8
10
--'!:~'---
t3 ........
14 tw'__
19
20
15 ~ -I
16 ~'~r
F-'-'J, ........
21
'---'~--
22
8 -j
V
Figure 3 G-banded representative karyotype of specimen No. 2 with abnormalities similar to specimen 1. Both chromosomes 16 in this tumor are normal. Translocations and terminal deletions were the most c o m m o n rearrangements although trisomy 12 and m o n o s o m y 17 were also present. Two p u l m o n a r y nodules (specimens 1 and 2 in Table 1) showed clonal abnormalities involving chromosome 3 at band p21. N o n r a n d o m i n v o l v e m e n t of this band is c o m m o n in small cell lung cancers [5] and mesotheliomas [6] and has led to the suggestion that it may be the site of the primary genetic change. Deletions of the short arm of chromosome 3 around band p21 have also been observed in renal cell carcinomas [8] and ovarian and breast cancers [9]. Abnormalities of 3p may therefore be associated with a n u m b e r of different tumorigenic events. Oncogenes SKI, ARG, and TRK have been mapped to the long arm of chromosome 1, NMYC and REL to the short arm of chromosome 2, HRAS1, and ST2, the tumor suppressor gene to 11p, HST, INT2, SEA, BCL1 and ETS1 to 11q, KRAS2, [NT1, and GLI to chromosome 12, FES to 15q, ERBA1, ERBB2, and NEU, and growth factors CSF3 and NGFR to 17q [7], the other chromosomes involved in rearrangements in this study. A n u m b e r of mechanisms, such as (1) activation and/ or overexpression of the genes at the chromosomal breakpoints, (2) loss of tumor suppressor genes through deletion of chromosomes, or (3) amplification of genes on chromosome 12 and 3p, the regions present in extra copy, may therefore have contributed to the progression of the tumor. Although the growth of alveolar sarcoma is relatively slow, the ultimate prognosis is k n o w n to be poor. A 5-year survival rate of 60%, a lO-year survial rate of 38%, and a 20-year survival rate of 15% have been reported for patients who present without metastases [10]. In most instances metastasis occurs early in the course of the disease. The patient in our study u n d e r w e n t resection of the primary tumor in November 1986, and by April 1989 had metastatic sarcoma to the lungs and brain. It is possible that the cytogenetic picture reflects the aggressive nature of the neoplasm; the role played by the chemotherapy given in 1987 is difficult to evaluate.
171
C h r o m o s o m e A b n o r m a l i t i e s i n A l v e o l a r Soft-Part S a r c o m a
Table 1
C y t o g e n e t i c f i n d i n g s i n t h e six m e t a s t a t i c p u l m o n a r y n o d u l e s
Specimen number
Tumor site
Culture time (days)
1.
Right lower lobe #1
4-5
2.
Right upper lobe # 2
4-5
3,
Right lower lobe #3
5-6
4. 5. 6,
Left lower lobe #1 Left upper lobe #2 Left lower lobe # 3
20 5
Karyotype 5: 46,XY 10: 47,XY,- 1, + der(1)t(3;1)(1;?)(3pter--, p21::1p36.1--~cen--~q32::?),del(2)(p12), del(10)(p11.2),del(11)(q14), + der(11), t ( l l ;?)(p11.2;?), + 1 2 , - 14, + der(14)t(14:?) (pl 1;?),- 15, + der(15)t(?;15)(15;2)(?::15p11-~ cen--~q25::2p 12--~2pter), 16, + der(16)t(1:16) (q12;q24),- 17 12: 46,XY 1: 45,X, Y 3: 47,XY, 1,+der(1)t(3;1)(1;?)(3pter~ p21::lp36.1---,cen---,q32::?),del(2)(p12), del(10)(pl 1.21.del(11)(q14), + der(11)t(31:?) (p11.2;?),+ 12, 14, + der(14)t(14;?) (p11;?), - 15, + der(15)t(?:15)(15;2)(?::15p11---~ cen--~q25::2p12----~2pter), - 17 16: 46,XY 1: 46,XY,t(16;21)(p11;q11) 20: 46,XY 15: 46,XY No growth
The authors thank Robert Roeder and Fred Flohrschutz for help with the illustrations and Shirley Frazzini for secretarial assistance. The work was supported in part by Contract No. N01-CP71018 from the National Cancer Institute.
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