SHORT COMMUNICATIONS Constitutional Translocation (8;13) in a Patient with Non-Hodgkin's Lymphoma Maria-Teresa Salles, Olimpia Neyra, Lucia Taja, Guadalupe Cervantes, Margarita Gagni re, Mabel Cerrillo, Alejandro Mohar, Alvaro Osornio, Eduardo Reynoso, Gina Gorodezky, and Pedro Sobrevilla-Calvo
ABSTRACT: We report a case of non-ltodgkin's lymphama in a 16-year-old male, whose peripheral white blood (:ells have a t(8;13)(q24;q14). There are no previous reports that describe this association. Although the tumor cells were not studied, we discuss the possible link between this finding and the development of the malignant lymphoma.
INTRODUCTION The importance of c h r o m o s o m e abnormalities in the development of h u m a n neoplasia is becoming more apparent [1]. The association of constitutional c h r o m o s o m e abnormalities with an increased risk of cancer is a well-described phenomenon. There is an association between Dawn's syndrome and acute leukemia [2], the del(13)(q14) with retinot)lastoma, and the del(11)(p13) with Wilrns' tumor [31. Also d o c u m e n t e d is the frequent finding of nonrandom (:hrom()some abnormalities m the neoplastic cells, like the Philad e l p h i a c h r o m o s o m e in chronic myelogenous leukemia, the t(14;18)(q32;q21) in follicular lymphoma, or the t(8;14)(q24:q32) in non-cleaved small cell l y m p h o m a [4]. In this paper we report what we considered to be the first case of a somatic t(8:13) in a patient with non-Hodgkin's lymphoma.
MATERIALS AND METHODS
cm retroperitoneal mass, c o n f r m e d by an abdominal CT scan. Laboratory findings revealed hemoglobin of 8.6 g/dL, white blood cell count 7.6 x 10 :~ cells/gL with a normal differential count, platelets 520 x IO'~/I~L. A bone marrow biopsy was normal. A trucut biopsy of the tumor showed a diffuse large cell non-Hodgkin's lymphoma. He received a total of 12 weeks of c h e m o t h e r a p y with the VACOP-B regimen (etoposide, adriamycin, c y c l o p h o s p h a m i d e , vincristine, prednisone, and bleomycin) [5], achieving a complete remission. He remained in good health until November 1990, 6 months after finishing treatment.
Metaphase Preparations A peripheral blood cytogenetic study was done before and after treatment. After a 72-hour peripheral blood culture, on RPMI-1640 with fetal calf serum and phytohemagglutinin stimulated, the cells were harvested with the conventional technique 161. Chromosome analysis was performed in 100 metaphases before treatment and 50 after completing chemotherapy using both G- and Q-banding techniques.
Case Report A 16-year-old male with a 1-year history of ",,,,eight loss and fever presented to the Department of Hematology at the Instituto Nacional de Cancerologia in Mexico City. There was no family history of neoplastic diseases. On physical examination, the only relevant finding was a huge 25 x 25From the Departments of Cytogenetics and ttematology. Insti|uto National de Cancerologia. Mexico City and the Department af Cytagenetics, Centro ltospitalaria 20 de Noviembre. ISSSTE, MOxico ('ity, MOxico. Submitted (is an abstract to the XVII Ameri(:an Society ol ('linical Ontology. Annual Meeting. Houston TX, May' 1991. Address reprint requests to: M. T. Salles, lnstituto National de Concerologia, Avenida San Fernando #22, Tlalpan, M~xico D.F. CP 14OOO. Received March 11, 1991; aecepted May 8. 1991.
Cytogenetic Findings Fifteen metaphases were karyotyped, finding a 46,XY,t(8;13)(q24;q'14) in all the metaphases studied, in both samples, shown in Figures 1 and 2. The translocation involving chromosomes [)ands 8q24 and 13q14 is showed in Figure 3.
DISCUSSION We presumed that the abnormality found was constitutional because it was present in all the peripheral blood ceils studied before and after treatment. Unfortunately, we did not have the o p p o r t u n i t y to study the tumor ceils. Although this association could only be due to chance, as is proposed by Benitez, who found a frequency of 1.25%
80 C a n c e r C]enet (~ytogenet 59:80 83 (1992) l} 165-460P,.92.'S05.00
:(" 1992 Elsevier S c i e n c e P u b l i s h h l g (]o., Inc. 655 A v e m l e o[ the A m e r i c a s . N e w York, NY 10010
19
13
6
1
15
3
9
4
21
16
10
5
22
17
11
t:r...,
18
12
Figure 1 G-banded karyotype with the t(8;13)(q24;q14). Arrows indicate rearranged chromosomes.
20
14
2
t,r
xy
Figure 2 Q-banded karyotype with the t(8;13}(q24;q14). Arrows indicate rearranged chromosomes.
t~
t(8:13) Associated with Non-Hodgkin's Lymphoma
83
in 13q14 is associated with the development of different neoplasias such as retinoblastoma, osteosarcoma, and lung cancer [8]. Therefore, we propose that the translocation (8:13) found in this patient could favor a close location of the c - m y c gene (8q24) and the RB gene (13q14), a relationship that may play a major role in the development of this lymphoid neoplasia. However, it also may be that one or both genes were normal and not deregulated and that our finding is, as mentioned before, due to chance. More stuciies at the molecular level are necessary to clarify this possible association.
I
REFERENCES
8 Figure 3 (q24;q141.
13
Partial karyotype showing the transloc:ation (8:131
of constitutional chromosome abnormalities in 718 patients with hematologic malignancies [7], we propose that the chromosome abnormality found in this patient could be playing a role in the development of the lymphoma. This is supported because in the case of lymphoma cells, the consistently reported chromosome abnormalities frequently involve chromosome 8, as in t(2;8)(p11-12;q24); t(8;14)(q24;q32): and t(8;22)(q24;q11) [4]. It is considered that this association could be due to the abnormal function of the c - m y c oncogene present in 8q24. On the other hand, it is also known that the deletion of the RB gene present
1. Pathak S [1989): Chromosomal changes in cancer. Cancer Bull 41(5]:281-282. 2. Holland WW, Doll R, Carter CO (1962): The mortality from leukemia and others cancers among patients with l)own's syndrome (mongols) and among their parents. Br J Cancer 16(2):177-186. 3. Kakati S [1989): Deletion of constitutional chromosome segment, loss of dominant allele and tumargenicity. Cancer Bull 41[5/:306-309. 4. Le Beau M (1990): Chromosomal abnormalities in non-Hodgkin's lymphomas. Semin Oncol 17(1):20-29. 5. Reynoso EE, Magallon VE, Sobrevilla PJ, Alexander IF, Andrade D (1989): VACOP-B for the treatment of diffuse aggressive lymphomas at the lnstituto Nacional de Cancerologfa, Mexico City. Blood (Suppl 1) 74:379a. 6. Moorhedd P, Nowell P(', Mellman W], Battips DM, Hugerford DA (1960): Chromosomal preparations of leukocytes cultured from human peripheral blood. Exp Cell Res 20:613-616. 7. Benitez J, Valcarcel E, Ramos C. Ayuso C, Cascos AS (1987): Frequency of constitutional c:hromosome alterations in patients with hematologic neoplasias. Cancer Genet Cytogenet 24: 345-354. 8. Klein G (1987): ]'he approaching era of the tumor suppressor genes. Science 238:1538-1545.
ABSTRACT: We report a case of non-ltodgkin's lymphama in a 16-year-old male, whose peripheral white blood (:ells have a t(8;13)(q24;q14). There are no previous reports that describe this association. Although the tumor cells were not studied, we discuss the possible link between this finding and the development of the malignant lymphoma.
INTRODUCTION The importance of c h r o m o s o m e abnormalities in the development of h u m a n neoplasia is becoming more apparent [1]. The association of constitutional c h r o m o s o m e abnormalities with an increased risk of cancer is a well-described phenomenon. There is an association between Dawn's syndrome and acute leukemia [2], the del(13)(q14) with retinot)lastoma, and the del(11)(p13) with Wilrns' tumor [31. Also d o c u m e n t e d is the frequent finding of nonrandom (:hrom()some abnormalities m the neoplastic cells, like the Philad e l p h i a c h r o m o s o m e in chronic myelogenous leukemia, the t(14;18)(q32;q21) in follicular lymphoma, or the t(8;14)(q24:q32) in non-cleaved small cell l y m p h o m a [4]. In this paper we report what we considered to be the first case of a somatic t(8:13) in a patient with non-Hodgkin's lymphoma.
MATERIALS AND METHODS
cm retroperitoneal mass, c o n f r m e d by an abdominal CT scan. Laboratory findings revealed hemoglobin of 8.6 g/dL, white blood cell count 7.6 x 10 :~ cells/gL with a normal differential count, platelets 520 x IO'~/I~L. A bone marrow biopsy was normal. A trucut biopsy of the tumor showed a diffuse large cell non-Hodgkin's lymphoma. He received a total of 12 weeks of c h e m o t h e r a p y with the VACOP-B regimen (etoposide, adriamycin, c y c l o p h o s p h a m i d e , vincristine, prednisone, and bleomycin) [5], achieving a complete remission. He remained in good health until November 1990, 6 months after finishing treatment.
Metaphase Preparations A peripheral blood cytogenetic study was done before and after treatment. After a 72-hour peripheral blood culture, on RPMI-1640 with fetal calf serum and phytohemagglutinin stimulated, the cells were harvested with the conventional technique 161. Chromosome analysis was performed in 100 metaphases before treatment and 50 after completing chemotherapy using both G- and Q-banding techniques.
Case Report A 16-year-old male with a 1-year history of ",,,,eight loss and fever presented to the Department of Hematology at the Instituto Nacional de Cancerologia in Mexico City. There was no family history of neoplastic diseases. On physical examination, the only relevant finding was a huge 25 x 25From the Departments of Cytogenetics and ttematology. Insti|uto National de Cancerologia. Mexico City and the Department af Cytagenetics, Centro ltospitalaria 20 de Noviembre. ISSSTE, MOxico ('ity, MOxico. Submitted (is an abstract to the XVII Ameri(:an Society ol ('linical Ontology. Annual Meeting. Houston TX, May' 1991. Address reprint requests to: M. T. Salles, lnstituto National de Concerologia, Avenida San Fernando #22, Tlalpan, M~xico D.F. CP 14OOO. Received March 11, 1991; aecepted May 8. 1991.
Cytogenetic Findings Fifteen metaphases were karyotyped, finding a 46,XY,t(8;13)(q24;q'14) in all the metaphases studied, in both samples, shown in Figures 1 and 2. The translocation involving chromosomes [)ands 8q24 and 13q14 is showed in Figure 3.
DISCUSSION We presumed that the abnormality found was constitutional because it was present in all the peripheral blood ceils studied before and after treatment. Unfortunately, we did not have the o p p o r t u n i t y to study the tumor ceils. Although this association could only be due to chance, as is proposed by Benitez, who found a frequency of 1.25%
80 C a n c e r C]enet (~ytogenet 59:80 83 (1992) l} 165-460P,.92.'S05.00
:(" 1992 Elsevier S c i e n c e P u b l i s h h l g (]o., Inc. 655 A v e m l e o[ the A m e r i c a s . N e w York, NY 10010
19
13
6
1
15
3
9
4
21
16
10
5
22
17
11
t:r...,
18
12
Figure 1 G-banded karyotype with the t(8;13)(q24;q14). Arrows indicate rearranged chromosomes.
20
14
2
t,r
xy
Figure 2 Q-banded karyotype with the t(8;13}(q24;q14). Arrows indicate rearranged chromosomes.
t~
t(8:13) Associated with Non-Hodgkin's Lymphoma
83
in 13q14 is associated with the development of different neoplasias such as retinoblastoma, osteosarcoma, and lung cancer [8]. Therefore, we propose that the translocation (8:13) found in this patient could favor a close location of the c - m y c gene (8q24) and the RB gene (13q14), a relationship that may play a major role in the development of this lymphoid neoplasia. However, it also may be that one or both genes were normal and not deregulated and that our finding is, as mentioned before, due to chance. More stuciies at the molecular level are necessary to clarify this possible association.
I
REFERENCES
8 Figure 3 (q24;q141.
13
Partial karyotype showing the transloc:ation (8:131
of constitutional chromosome abnormalities in 718 patients with hematologic malignancies [7], we propose that the chromosome abnormality found in this patient could be playing a role in the development of the lymphoma. This is supported because in the case of lymphoma cells, the consistently reported chromosome abnormalities frequently involve chromosome 8, as in t(2;8)(p11-12;q24); t(8;14)(q24;q32): and t(8;22)(q24;q11) [4]. It is considered that this association could be due to the abnormal function of the c - m y c oncogene present in 8q24. On the other hand, it is also known that the deletion of the RB gene present
1. Pathak S [1989): Chromosomal changes in cancer. Cancer Bull 41(5]:281-282. 2. Holland WW, Doll R, Carter CO (1962): The mortality from leukemia and others cancers among patients with l)own's syndrome (mongols) and among their parents. Br J Cancer 16(2):177-186. 3. Kakati S [1989): Deletion of constitutional chromosome segment, loss of dominant allele and tumargenicity. Cancer Bull 41[5/:306-309. 4. Le Beau M (1990): Chromosomal abnormalities in non-Hodgkin's lymphomas. Semin Oncol 17(1):20-29. 5. Reynoso EE, Magallon VE, Sobrevilla PJ, Alexander IF, Andrade D (1989): VACOP-B for the treatment of diffuse aggressive lymphomas at the lnstituto Nacional de Cancerologfa, Mexico City. Blood (Suppl 1) 74:379a. 6. Moorhedd P, Nowell P(', Mellman W], Battips DM, Hugerford DA (1960): Chromosomal preparations of leukocytes cultured from human peripheral blood. Exp Cell Res 20:613-616. 7. Benitez J, Valcarcel E, Ramos C. Ayuso C, Cascos AS (1987): Frequency of constitutional c:hromosome alterations in patients with hematologic neoplasias. Cancer Genet Cytogenet 24: 345-354. 8. Klein G (1987): ]'he approaching era of the tumor suppressor genes. Science 238:1538-1545.
