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Abnormalities of chromosome No. 1: Two cases with lymphocytic lymphomas
Abnormalities of Chromosome No. 1: Two Cases with Lymphocytic Lymphomas Irma Slavutsky, Mabel Labal de Vinuesa, Juan Dupont, Nora Mondini, and Sonia Brieux de Salum
ABSTRACT: Two cases of lymphocytic lymphoma with a duplication of part of the long arm of chromosome #I, between bands lq25 and lq32, are presented. The coincidence between this finding with others in the literature supports the concept that this specific chromosome segment is related to the proliferative advantage of malignant cells in neoplasia.
INTRODUCTION
The application of chromosome b a n d i n g technique to the study of malignant lymphomas has shown that some of the abnormalities observed are not random. Many publications indicate the frequent finding of markers 14q+, l p - , 11q-, 9q-, 18q-, 3 q - and 8q-, trisomies of chromosomes #3, # 7 and #18, and monosomies of chromosomes # 8 and #15 in l y m p h o i d malignancies [ 1 - 3]. At present, the observations suggest that specific regions of these chromosomes are involved in these changes [4]. Here we describe the karyotypes seen in two lymphocytic lymphomas in which a duplication of part of the long arm of chromosome #1 between bands lq25 and lq32 was observed.
CLINICAL REPORTS
Case 1
E. Z., a 58-year-old female, was admitted to this Institution in February 1979 with multiple l y m p h node enlargement. She had a previous history of fever, arthralgia, weight loss, and the appearance of skin tumors on the back for at least one year. She had a normal chest X-ray and her biochemistries and hematological data were unremarkable. A supraclavicular l y m p h node was biopsied and its histopathologic feature was poorly differentiated lymphocytic l y m p h o m a diffuse (PDLL-D) according to Rappaport's classification [5]. Her stage was IV-A of the A n n Arbor classification [6]. From the Tissue Cultureand CytogeneticDepartmentof the HematologfcResearch Institute "MarianoR Castex". NationalAcademyof Medicine,BuenosAires, Argentina. Address requests for reprints to: Dr. Irma Slavatsky, Departamento de Cultivo de Tejidos y Citogen6tica, Instituto de Investigaciones Hematol6gicas, Academia Nacional de Medicina, Av. Las Heras 3092 (1425), Capital Federal, Buenos Aires, Rephblica Argentina. Received May 21, 1980; accepted November 19, 1980.
341 © ElsevierNorth Holland,Inc., 1981 52 VanderbiltAve., New York, NY 1 0 0 1 7
Cancer Geneticsand Cytogenetics3, 341- 346 (1981) 0165-4608/81/043410652.50
342
I. Slavutsky et al. She was started on c h e m o t h e r a p y (COPP: c y c l o p h o s p h a m i d e , vincristine, procarbazine, prednisone) in February 1979 for 6 months. Two months after discontinuing chemotherapy, she relapsed with skin tumors and enlargement of the l y m p h nodes. She was started on ABVD (Adriamycin, bleomycin, vinblastine, dacarbazine) and at present is in good clinical condition.
Case 2
M.A., a 32-year-old female, was referred to this Institution in November 1979. She had a previous history of neck, axillary, and inguinal l y m p h node and spleen enlargements. At the time of admission, the physical examination revealed the cervical and axillary l y m p h nodes to be enlarged. The liver was p a l p a b l e 2 cm and the spleen 14 cm below the costal margin. No other physical findings were present. Her chest X-ray film was normal, as well as her biochemistries. Hematological data were Hb 12.16 g/d, WBC 11,500/mm :~, differential polymorphonuclears 46%, l y m p h o c y t e s 50%, monocytes 2%, eosinophils 2%, and platelet count 128,000/mm 3. A cervical l y m p h node biopsy was performed and the histopathologic diagnosis was well differentiated l y m p h o c y t i c l y m p h o m a - n o d u l a r (WDLL-N), according to Rappaport's classification [5]. As her l y m p h a n g i o g r a p h y was strikingly pathologic, and bone marrow and liver biopsies showed significant l y m p h o c y t i c infiltration, her stage was assessed to be 1V-A of the A n n Arbor classification [6]. She was started on c y c l o p h o s p h a m i d e , 250 mg/day, for 5 days every three weeks. After 5 months of treatment, the l y m p h node enlargement disappeared, the liver and spleen showed a remarkable reduction in size and bone marrow aspiration was normal. CYTOGENETIC STUDIES
In both cases, chromosome analysis was performed on cells from biopsied l y m p h nodes involved with l y m p h o c y t i c l y m p h o m a . Tissues were m i n c e d with scissors in a petri dish containing m e d i u m F-IO with 15% fetal calf serum. The cells were agitated by pipetting and the cell suspension inoculated into several Erlenmeyer flasks. Chromosomes from these cells were prepared directly and after short-term (24 - 4 8 hr) culture in the same m e d i u m at 37°C. Mitotic cells were a c c u m u l a t e d by exposure to Colcemid (0.1 txg/ml medium) for 30 min before harvest. They were treated in a hypotonic solution of 0.075 M KC1 for 20 min at 37°C, fixed once in m e t h a n o l : a c e t i c acid (3 : 1) solution and twice in a 1 : 1 solution, and air dried. Chromosome preparations were stained with conventional Giemsa or b a n d e d
Table 1
Chromosome counts Chromosomes no.
Case no. 1 2
Karyotyped cells/ 41 42 43 44 45 46 47 48 total analyzed cells 2
1 1
1 1
3 2
1 3
13 15
9 5
2 1
9/30 11/30
343
Abnormalities of Chromosome No. 1
) ; ;: ,q
1 Figure 1
2
3
Partial karyotype of two G-banded cells in case 1.
with trypsin-Giemsa [7]. Chromosomal heterochromatin was e x a m i n e d by a C-banding technique [8]. Identification of the c h r o m o s o m e s according to the Paris nomenclature [9] was achieved by using photographs of the metaphases.
RESULTS
Case 1
Thirty cells from a l y m p h node were analyzed; the c h r o m o s o m e count is shown in Table 1. A clone with 47 chromosomes with a l q ÷ marker (I) and c o m p l e t e trisomy of c h r o m o s o m e #3 (Fig 1) were seen. This marker originated through the d u p l i c a t i o n of the long arm of c h r o m o s o m e #1 between bands lq21 and lq32 (Fig. 2).
Figure 2
Marker I and normal chromosome #1 (with diagrammatic presentation) of case 1.
1(~+
1
344
I. Slavutsky et al. Table 2
Stem line karyotypes and characterization of markers
Case no.
Stem line karyotype
1
46,XX,1q+(l)?+3/ 46,XX 46,XX,lp+(I) 14q+{II)/47,XX, 1p+(I),14q+[II),+9
2
Marker no. l-lq+ I-lp+ II-14q+
Mode of origin der(1),dup(1),(1 p t e r ~ l q32 :: 1q21-~lqter) t(1;1)(1qter-~lq25 :: lp36~lqter) t[14;?)(14pter~14q32 : : ?)
Of the 13 cells with 46 chromosomes (Table 1), 8 presented a normal karyotype, 46,XX, whereas the remaining ones had the anomalies of the clone already described, with r a n d o m c h r o m o s o m e losses. Case 2
Thirty cells were also analyzed in this case and the h e t e r o p l o i d y range is shown in Table 1. No normal cells were observed. All of the cells had two marker chromosomes, l p + (marker I) and 14q+ (marker II) (Table 2). Marker I was an abnormal c h r o m o s o m e #1 w h i c h originated by d u p l i c a t i o n and translocation of part of the long arm of this c h r o m o s o m e between bands lq25 and 1q44, and joined to the short arm at band l p 3 6 (Fig. 3A). Marker II had a dark extra band of u n k n o w n origin on its long arm with the break point at 14q32 (Fig. 3B). Besides markers I and II, a subclone of cells with 47 chromosomes, due to +9, was observed. The C-banding technique showed a normal banding pattern in both cases. DISCUSSION
Chromosome #1 is involved in different malignancies: breast carcinoma [10], colonic cancer [11], m e l a n o m a [12], cervical carcinoma [13, 14] and m y e l o m a [/5]. Rowley [4] found long arm d u p l i c a t i o n of c h r o m o s o m e #1 in 35 patients with hematologic disorders (nonlymphocytic acute leukemia, p o l y c y t h e m i a vera, and myelofibrosis). In all cases a trisomy between bands l q 2 5 - lq32 was observed, w h i c h could be related to an increased malignant potential in solid tumors as well as in hematologic malignancies. It must be pointed out that c h r o m o s o m e #1 is altered rather frequently in lymp h o i d neoplasms [16], with the following abnormalities having been observed: l p - , most often with break points at 1 p 2 1 - 1 p 2 2 ; l q - with break points usually at 1 q 2 1 - 1 q 2 3 and i(lq) (3). Fukuhara [17] described a d u p l i c a t i o n of part of the long arm of chromosome #1 in a case of histiocytic l y m p h o m a . In this article we have described two cases of l y m p h o c y t i c l y m p h o m a with duplication of part of the long arm of chromosome #1. In the first case, marker I (lq+), with d u p l i c a t i o n between lq21 and lq32, was present in 73% of the analyzed cells, forming a clone with 47 chromosomes due to the presence of trisomy of c h r o m o s o m e #3. This a n o m a l y has already been observed in l y m p h o m a s [3]. The cells with a normal karyotype could be due to the presence of nonneoplastic cells in division or remnants of an original stem line without abnormalities [18]. In case 2, marker I could be the result of a c o m p l e x rearrangement in the course of clonal evolution. Marker II is the most frequently found anomaly in l y m p h o m a s [3, 16, 19]. The break point was at band 14q32, but it was impossible to determine the origin of the extra
345
A b n o r m a l i t i e s of C h r o m o s o m e No. 1
.I
b
14q÷
14
B
1
1
Figure 3
Case 2. (A) Marker I and normal chromosome #1 with diagrammatic presentation. (B) Marker II and normal chromosome #14 with diagrammatic presentation.
m a t e r i a l , as n o o t h e r c h r o m o s o m e s p r e s e n t e d a l t e r a t i o n of t h e b a n d i n g p a t t e r n . 16.6% of t h e a n a l y z e d cells f o r m e d a s u b c l o n e i n w h i c h a t r i s o m y of c h r o m o s o m e # 9 w a s o b s e r v e d i n a d d i t i o n to t h e t w o m a r k e r s . E v e n t h o u g h , t h e e x t e n t of t h e d u p l i c a t e d r e g i o n w a s n o t e x a c t l y t h e s a m e i n b o t h cases, t h e d u p l i c a t i o n b e t w e e n l q 2 5 a n d l q 3 2 w a s a c o m m o n f e a t u r e of t h e c e l l s of t h e s e t w o p a t i e n t s . T h e c o i n c i d e n c e of t h e f i n d i n g s i n b o t h c a s e s (in stage IV of t h e d i s e a s e ) , w o u l d s u p p o r t t h e c o n c e p t t h a t a s p e c i f i c c h r o m o s o m e s e g m e n t m a y b e r e l a t e d to t h e prolife r a t i v e a d v a n t a g e of m a l i g n a n t c e l l s i n n e o p l a s i a . Supported by grants from CONICET (Consejo Nacional de Investigaciones Cientificas y T6cnicas). The authors acknowledge the valuable technical assistance of Mrs. Estela de Licen and Miss. Diana Massa and the photographic work of Mr. Osvaldo Miskoski.
REFERENCES 1. Fukuhara S, Rowley JD (1980): Chromosome 14 translocations in non-Burkitt lymphomas. Int J Cancer 22, 1 4 - 21. 2. Fukuhara S, Rowley JD, Variakojis D, Golomb HM (1979): Chromosome abnormalities in poorly differentiated lymphocytic lymphoma. Cancer Res 39, 3119 - 3128. 3. Mark J, Dahlenfors R, Ekedahl C /1979): Recurrent chromosomal aberrations in nonHodgkin and non-Burkitt lymphomas. Cancer Genet Cytogenet 1, 3 9 - 5 6 . 4. Rowley JD (1978): Abnormalities of chromosome No. 1: significance in malignant transformation. Virchows Arch B Cell Pathol 29, 139-144. 5. Rappaport H (1966): Tumors of the hematopoietic system. In: Atlas of Tumor Pathology, Sect. III, Fasc 8. Armed Forces Institute of Pathology, Washington DC. 6. Carbone PP, Kaplan HS, Musshoff K, Smithers DW, Tubiana M (1972): Report of the Commitee on Hodgkin's disease staging classification. Cancer Res 31:1860 - 1861. 7. Seabright M (1971): Rapid banding technique for h u m a n chromosomes. Lancet 2 , 9 7 1 - 9 7 2 . 8. Sumner AT (1972): A simple technique for demonstrating centromeric heterochromatin. Exp Cell Res 75, 304-306.
346
I. S l a v u t s k y et al.
9. Paris Conference (1971): Standardization in Human Cytogenetics. Birth Defects: Original Article Series, VIII: 7, 1972. The National Foundation, New York. 10. Cruciger QVJ, Pathak S, Cailleau R (1976): Human breast carcinomas: marker chromosomes involving lq in seven cases. Cytogenet Cell Genet 17,231 - 235. 11. Kovacs G (1978): Duplicated parts of chromosome No. 1 in primary cancers. Lancet 1,554. 12. Kakati S, Song SY, Sandberg AA (1977): Chromosomes and causation of human cancer and leukemia XXII. Karyotypic changes in malignant melanoma. Cancer 40, 1173 - 1181. 13. Atkin NB, Baker MC (1977): Chromosome 1 in cervical carcinoma. Lancet 2,989. 14. Atkin NB, Baker MC (1979): Chromosome 1 in 26 carcinomas of the cervix uteri: Structural and numerical changes. Cancer 44,604-613. 15. Liang W, Hopper JE, Rowley JD (1979): Karyotypic abnormalities and clinical aspects of patients with multiple myeloma and related paraproteinemic disorders. Cancer 44,630 - 644. 16. Mark J, Ekedahl C, Dahlenfors R (1978): Characteristics of the banding patterns in nonHodgkin and non-Burkitt lymphomas. Hereditas 88, 229- 242. 17. Fukuhara S, Rowley JD, Variakojis D, Sweet LD Jr (1978): Banding studies on chromosomes in diffuse "Histiocytic" lymphomas: correlation of 14q+ marker chromosome with cytology. Blood 52,989-1002. 18. Wiener F, Ohno S, Spira J, Haran-Ghera N, Klein G (1978): Chromosome changes (trisomies No. 15 and 17) associated with tumor progression in leukemias induced by radiation leukemia virus. J Natl Cancer Inst 60,227-237. 19. Fukuhara S (1978): Significance of 14q translocation in non-Hodgkin lymphomas. Virchows Arch B Cell Pathol 29, 99 - 106.
ABSTRACT: Two cases of lymphocytic lymphoma with a duplication of part of the long arm of chromosome #I, between bands lq25 and lq32, are presented. The coincidence between this finding with others in the literature supports the concept that this specific chromosome segment is related to the proliferative advantage of malignant cells in neoplasia.
INTRODUCTION
The application of chromosome b a n d i n g technique to the study of malignant lymphomas has shown that some of the abnormalities observed are not random. Many publications indicate the frequent finding of markers 14q+, l p - , 11q-, 9q-, 18q-, 3 q - and 8q-, trisomies of chromosomes #3, # 7 and #18, and monosomies of chromosomes # 8 and #15 in l y m p h o i d malignancies [ 1 - 3]. At present, the observations suggest that specific regions of these chromosomes are involved in these changes [4]. Here we describe the karyotypes seen in two lymphocytic lymphomas in which a duplication of part of the long arm of chromosome #1 between bands lq25 and lq32 was observed.
CLINICAL REPORTS
Case 1
E. Z., a 58-year-old female, was admitted to this Institution in February 1979 with multiple l y m p h node enlargement. She had a previous history of fever, arthralgia, weight loss, and the appearance of skin tumors on the back for at least one year. She had a normal chest X-ray and her biochemistries and hematological data were unremarkable. A supraclavicular l y m p h node was biopsied and its histopathologic feature was poorly differentiated lymphocytic l y m p h o m a diffuse (PDLL-D) according to Rappaport's classification [5]. Her stage was IV-A of the A n n Arbor classification [6]. From the Tissue Cultureand CytogeneticDepartmentof the HematologfcResearch Institute "MarianoR Castex". NationalAcademyof Medicine,BuenosAires, Argentina. Address requests for reprints to: Dr. Irma Slavatsky, Departamento de Cultivo de Tejidos y Citogen6tica, Instituto de Investigaciones Hematol6gicas, Academia Nacional de Medicina, Av. Las Heras 3092 (1425), Capital Federal, Buenos Aires, Rephblica Argentina. Received May 21, 1980; accepted November 19, 1980.
341 © ElsevierNorth Holland,Inc., 1981 52 VanderbiltAve., New York, NY 1 0 0 1 7
Cancer Geneticsand Cytogenetics3, 341- 346 (1981) 0165-4608/81/043410652.50
342
I. Slavutsky et al. She was started on c h e m o t h e r a p y (COPP: c y c l o p h o s p h a m i d e , vincristine, procarbazine, prednisone) in February 1979 for 6 months. Two months after discontinuing chemotherapy, she relapsed with skin tumors and enlargement of the l y m p h nodes. She was started on ABVD (Adriamycin, bleomycin, vinblastine, dacarbazine) and at present is in good clinical condition.
Case 2
M.A., a 32-year-old female, was referred to this Institution in November 1979. She had a previous history of neck, axillary, and inguinal l y m p h node and spleen enlargements. At the time of admission, the physical examination revealed the cervical and axillary l y m p h nodes to be enlarged. The liver was p a l p a b l e 2 cm and the spleen 14 cm below the costal margin. No other physical findings were present. Her chest X-ray film was normal, as well as her biochemistries. Hematological data were Hb 12.16 g/d, WBC 11,500/mm :~, differential polymorphonuclears 46%, l y m p h o c y t e s 50%, monocytes 2%, eosinophils 2%, and platelet count 128,000/mm 3. A cervical l y m p h node biopsy was performed and the histopathologic diagnosis was well differentiated l y m p h o c y t i c l y m p h o m a - n o d u l a r (WDLL-N), according to Rappaport's classification [5]. As her l y m p h a n g i o g r a p h y was strikingly pathologic, and bone marrow and liver biopsies showed significant l y m p h o c y t i c infiltration, her stage was assessed to be 1V-A of the A n n Arbor classification [6]. She was started on c y c l o p h o s p h a m i d e , 250 mg/day, for 5 days every three weeks. After 5 months of treatment, the l y m p h node enlargement disappeared, the liver and spleen showed a remarkable reduction in size and bone marrow aspiration was normal. CYTOGENETIC STUDIES
In both cases, chromosome analysis was performed on cells from biopsied l y m p h nodes involved with l y m p h o c y t i c l y m p h o m a . Tissues were m i n c e d with scissors in a petri dish containing m e d i u m F-IO with 15% fetal calf serum. The cells were agitated by pipetting and the cell suspension inoculated into several Erlenmeyer flasks. Chromosomes from these cells were prepared directly and after short-term (24 - 4 8 hr) culture in the same m e d i u m at 37°C. Mitotic cells were a c c u m u l a t e d by exposure to Colcemid (0.1 txg/ml medium) for 30 min before harvest. They were treated in a hypotonic solution of 0.075 M KC1 for 20 min at 37°C, fixed once in m e t h a n o l : a c e t i c acid (3 : 1) solution and twice in a 1 : 1 solution, and air dried. Chromosome preparations were stained with conventional Giemsa or b a n d e d
Table 1
Chromosome counts Chromosomes no.
Case no. 1 2
Karyotyped cells/ 41 42 43 44 45 46 47 48 total analyzed cells 2
1 1
1 1
3 2
1 3
13 15
9 5
2 1
9/30 11/30
343
Abnormalities of Chromosome No. 1
) ; ;: ,q
1 Figure 1
2
3
Partial karyotype of two G-banded cells in case 1.
with trypsin-Giemsa [7]. Chromosomal heterochromatin was e x a m i n e d by a C-banding technique [8]. Identification of the c h r o m o s o m e s according to the Paris nomenclature [9] was achieved by using photographs of the metaphases.
RESULTS
Case 1
Thirty cells from a l y m p h node were analyzed; the c h r o m o s o m e count is shown in Table 1. A clone with 47 chromosomes with a l q ÷ marker (I) and c o m p l e t e trisomy of c h r o m o s o m e #3 (Fig 1) were seen. This marker originated through the d u p l i c a t i o n of the long arm of c h r o m o s o m e #1 between bands lq21 and lq32 (Fig. 2).
Figure 2
Marker I and normal chromosome #1 (with diagrammatic presentation) of case 1.
1(~+
1
344
I. Slavutsky et al. Table 2
Stem line karyotypes and characterization of markers
Case no.
Stem line karyotype
1
46,XX,1q+(l)?+3/ 46,XX 46,XX,lp+(I) 14q+{II)/47,XX, 1p+(I),14q+[II),+9
2
Marker no. l-lq+ I-lp+ II-14q+
Mode of origin der(1),dup(1),(1 p t e r ~ l q32 :: 1q21-~lqter) t(1;1)(1qter-~lq25 :: lp36~lqter) t[14;?)(14pter~14q32 : : ?)
Of the 13 cells with 46 chromosomes (Table 1), 8 presented a normal karyotype, 46,XX, whereas the remaining ones had the anomalies of the clone already described, with r a n d o m c h r o m o s o m e losses. Case 2
Thirty cells were also analyzed in this case and the h e t e r o p l o i d y range is shown in Table 1. No normal cells were observed. All of the cells had two marker chromosomes, l p + (marker I) and 14q+ (marker II) (Table 2). Marker I was an abnormal c h r o m o s o m e #1 w h i c h originated by d u p l i c a t i o n and translocation of part of the long arm of this c h r o m o s o m e between bands lq25 and 1q44, and joined to the short arm at band l p 3 6 (Fig. 3A). Marker II had a dark extra band of u n k n o w n origin on its long arm with the break point at 14q32 (Fig. 3B). Besides markers I and II, a subclone of cells with 47 chromosomes, due to +9, was observed. The C-banding technique showed a normal banding pattern in both cases. DISCUSSION
Chromosome #1 is involved in different malignancies: breast carcinoma [10], colonic cancer [11], m e l a n o m a [12], cervical carcinoma [13, 14] and m y e l o m a [/5]. Rowley [4] found long arm d u p l i c a t i o n of c h r o m o s o m e #1 in 35 patients with hematologic disorders (nonlymphocytic acute leukemia, p o l y c y t h e m i a vera, and myelofibrosis). In all cases a trisomy between bands l q 2 5 - lq32 was observed, w h i c h could be related to an increased malignant potential in solid tumors as well as in hematologic malignancies. It must be pointed out that c h r o m o s o m e #1 is altered rather frequently in lymp h o i d neoplasms [16], with the following abnormalities having been observed: l p - , most often with break points at 1 p 2 1 - 1 p 2 2 ; l q - with break points usually at 1 q 2 1 - 1 q 2 3 and i(lq) (3). Fukuhara [17] described a d u p l i c a t i o n of part of the long arm of chromosome #1 in a case of histiocytic l y m p h o m a . In this article we have described two cases of l y m p h o c y t i c l y m p h o m a with duplication of part of the long arm of chromosome #1. In the first case, marker I (lq+), with d u p l i c a t i o n between lq21 and lq32, was present in 73% of the analyzed cells, forming a clone with 47 chromosomes due to the presence of trisomy of c h r o m o s o m e #3. This a n o m a l y has already been observed in l y m p h o m a s [3]. The cells with a normal karyotype could be due to the presence of nonneoplastic cells in division or remnants of an original stem line without abnormalities [18]. In case 2, marker I could be the result of a c o m p l e x rearrangement in the course of clonal evolution. Marker II is the most frequently found anomaly in l y m p h o m a s [3, 16, 19]. The break point was at band 14q32, but it was impossible to determine the origin of the extra
345
A b n o r m a l i t i e s of C h r o m o s o m e No. 1
.I
b
14q÷
14
B
1
1
Figure 3
Case 2. (A) Marker I and normal chromosome #1 with diagrammatic presentation. (B) Marker II and normal chromosome #14 with diagrammatic presentation.
m a t e r i a l , as n o o t h e r c h r o m o s o m e s p r e s e n t e d a l t e r a t i o n of t h e b a n d i n g p a t t e r n . 16.6% of t h e a n a l y z e d cells f o r m e d a s u b c l o n e i n w h i c h a t r i s o m y of c h r o m o s o m e # 9 w a s o b s e r v e d i n a d d i t i o n to t h e t w o m a r k e r s . E v e n t h o u g h , t h e e x t e n t of t h e d u p l i c a t e d r e g i o n w a s n o t e x a c t l y t h e s a m e i n b o t h cases, t h e d u p l i c a t i o n b e t w e e n l q 2 5 a n d l q 3 2 w a s a c o m m o n f e a t u r e of t h e c e l l s of t h e s e t w o p a t i e n t s . T h e c o i n c i d e n c e of t h e f i n d i n g s i n b o t h c a s e s (in stage IV of t h e d i s e a s e ) , w o u l d s u p p o r t t h e c o n c e p t t h a t a s p e c i f i c c h r o m o s o m e s e g m e n t m a y b e r e l a t e d to t h e prolife r a t i v e a d v a n t a g e of m a l i g n a n t c e l l s i n n e o p l a s i a . Supported by grants from CONICET (Consejo Nacional de Investigaciones Cientificas y T6cnicas). The authors acknowledge the valuable technical assistance of Mrs. Estela de Licen and Miss. Diana Massa and the photographic work of Mr. Osvaldo Miskoski.
REFERENCES 1. Fukuhara S, Rowley JD (1980): Chromosome 14 translocations in non-Burkitt lymphomas. Int J Cancer 22, 1 4 - 21. 2. Fukuhara S, Rowley JD, Variakojis D, Golomb HM (1979): Chromosome abnormalities in poorly differentiated lymphocytic lymphoma. Cancer Res 39, 3119 - 3128. 3. Mark J, Dahlenfors R, Ekedahl C /1979): Recurrent chromosomal aberrations in nonHodgkin and non-Burkitt lymphomas. Cancer Genet Cytogenet 1, 3 9 - 5 6 . 4. Rowley JD (1978): Abnormalities of chromosome No. 1: significance in malignant transformation. Virchows Arch B Cell Pathol 29, 139-144. 5. Rappaport H (1966): Tumors of the hematopoietic system. In: Atlas of Tumor Pathology, Sect. III, Fasc 8. Armed Forces Institute of Pathology, Washington DC. 6. Carbone PP, Kaplan HS, Musshoff K, Smithers DW, Tubiana M (1972): Report of the Commitee on Hodgkin's disease staging classification. Cancer Res 31:1860 - 1861. 7. Seabright M (1971): Rapid banding technique for h u m a n chromosomes. Lancet 2 , 9 7 1 - 9 7 2 . 8. Sumner AT (1972): A simple technique for demonstrating centromeric heterochromatin. Exp Cell Res 75, 304-306.
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9. Paris Conference (1971): Standardization in Human Cytogenetics. Birth Defects: Original Article Series, VIII: 7, 1972. The National Foundation, New York. 10. Cruciger QVJ, Pathak S, Cailleau R (1976): Human breast carcinomas: marker chromosomes involving lq in seven cases. Cytogenet Cell Genet 17,231 - 235. 11. Kovacs G (1978): Duplicated parts of chromosome No. 1 in primary cancers. Lancet 1,554. 12. Kakati S, Song SY, Sandberg AA (1977): Chromosomes and causation of human cancer and leukemia XXII. Karyotypic changes in malignant melanoma. Cancer 40, 1173 - 1181. 13. Atkin NB, Baker MC (1977): Chromosome 1 in cervical carcinoma. Lancet 2,989. 14. Atkin NB, Baker MC (1979): Chromosome 1 in 26 carcinomas of the cervix uteri: Structural and numerical changes. Cancer 44,604-613. 15. Liang W, Hopper JE, Rowley JD (1979): Karyotypic abnormalities and clinical aspects of patients with multiple myeloma and related paraproteinemic disorders. Cancer 44,630 - 644. 16. Mark J, Ekedahl C, Dahlenfors R (1978): Characteristics of the banding patterns in nonHodgkin and non-Burkitt lymphomas. Hereditas 88, 229- 242. 17. Fukuhara S, Rowley JD, Variakojis D, Sweet LD Jr (1978): Banding studies on chromosomes in diffuse "Histiocytic" lymphomas: correlation of 14q+ marker chromosome with cytology. Blood 52,989-1002. 18. Wiener F, Ohno S, Spira J, Haran-Ghera N, Klein G (1978): Chromosome changes (trisomies No. 15 and 17) associated with tumor progression in leukemias induced by radiation leukemia virus. J Natl Cancer Inst 60,227-237. 19. Fukuhara S (1978): Significance of 14q translocation in non-Hodgkin lymphomas. Virchows Arch B Cell Pathol 29, 99 - 106.