Chromosomal Abnormalities in Patients With Hodgkin's Disease: Evidence for Frequent Involvement of the 14q Chromosomal Region but Infrequent bcl-2 Gene Rearrangement in Reed-Sternberg Cells
Background : Rearrangements of the bcl-2 gene (also known as BCL2) have been detected in up to 40% of cases of Hodgkin's disease, and it has been speculated that such rearrangements may have a role in the pathogenesis of Hodgkin's disease. Purpose : The purposes of this study were ( a ) to assess the frequency of clonal chromosomal abnormalities in Hodgkin's disease, ( b ) to identify recurrent changes, ( c ) to determine whether the bcl-2 gene rearrangement was present in Reed-Sternberg cells (the neoplastic cells of Hodgkin's disease) and their variants, and ( d ) to analyze whether the presence of t(14;18) translocations in Reed-Sternberg cells explains the observed bcl-2 gene rearrangements in Hodgkin's disease. Methods : A cytogenetic study was performed on biopsy specimens from 28 consecutive untreated patients with Hodgkin's disease. The same patients were analyzed for bcl-2 gene rearrangement by a polymerase chain reaction (PCR) technique. To ascertain whether the abnormal karyotypes were present in and restricted to Reed-Sternberg cells, we also performed in situ hybridization with chromosome-specific probes. Results : Abnormal metaphases were identified in 23 of the 28 patients. In 11 patients, the chromosome 14q region was abnormal; in six of these patients, there was involvement of the 14q32 region that comprises the gene encoding for heavy-chain immunoglobulin. Only one patient had a t(14;18) translocation, whereas almost 40% of these 28 patients showed bcl-2 gene rearrangements by a PCR method. The in situ hybridization method showed that the abnormal karyotype was present in and restricted to Reed-Sternberg cells. Conclusions : We conclude that the majority of cases of Hodgkin's disease contain a clonal population with an abnormal karyotype, comprising the Reed-Sternberg cells. The q32 region of chromosome 14 is frequently involved, but a t(14;18) translocation is extremely infrequent. The occurrence of a bcl-2 gene rearrangement in Hodgkin's disease most likely results from the presence of sporadic, small bystander B lymphocytes that carry the translocation and that also can be frequently detected in reactive lymphoid tissue such as tonsils. Also, a range of different chromosomal translocations may provide growth or survival advantages to Reed-Sternberg cells. [J Natl Cancer Inst 84:1789–1793, 1992]