We have investigated the genetics of Burkitt's lymphoma, a malignancy of B cells affecting predominantly children. We have found that in Burkitt's lymphomas with the t(8;14) translocation the c-myc oncogene translocates from its normal position on band q24 of chromosome 8 to the heavy chain locus on chromosome 14. We have also shown that in the variant t(8;22) and t(2;8) translocations the c-myc gene remains on chromosome 8 and the chromosomal breaks are distal (3') to the c-myc oncogene. In these cases, the genes for immunoglobulin light chains translocate to a region 3' (distal) to the untranslocated and germline c-myc gene. The consequences of these three different translocations are the same: deregulation of the transcription of the involved c-myc oncogene. Such deregulation occurs at a restricted window of differentiation within the B-cell lineage. We are attempting to define the genetic elements within the three immunoglobulin loci which are responsible for the enhancement of c-myc trnascription in Burkitt's lymphoma. We have also studied B-cell lymphomas of adults, chronic lymphocytic leukemia of the B-cell type, and multiple myeloma in man. Such B-cell malignancies also carry translocations involving the heavy chain locus. We have cloned the breakpoints of both the t(11;14) and t(14;18) translocations occurring in B-cell neoplasia and have identified two genes for which we proposed the name of bcl-1 (B-cell leukemia/lymphoma 1) and bc1-2, which are located on band q13 of chromosome 11 and band q21 of chromosome 18, respectively, and are activated by their proximity to enhancer elements present in the heavy chain locus. We intend to characterize these two genes and their gene products, to determine their physiologic role, and to establish their role in neoplasia. We are also involved in studies to characterize the chromosomal breakpoints of acute promyelocytic leukemia (t(15;17) translocation), chronic myelogenous leukemia (t(9;22) translocation), Ph positive acute lymphocytic leukemia (t(9;22) translocation), acute myelogenous leukemia (t(8;22) translocation), and Ewing Sarcoma (t(11;22) translocation) and to detemine the role of genes flanking the breakpoints in the pathogenesis of these diseases. (Y)

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National Cancer Institute (NCI)
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Wistar Institute
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Kuroki, Tamotsu; Trapasso, Francesco; Yendamuri, Sai et al. (2003) Promoter hypermethylation of RASSF1A in esophageal squamous cell carcinoma. Clin Cancer Res 9:1441-5
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