BCL2 OVEREXPRESSION ASSOCIATED WITH CHROMOSOMAL AMPLIFICATION IN DIFFUSE LARGE B-CELL LYMPHOMA

Gene activation by translocation between an oncogene and an immunoglob ulin heavy-chain gene, which leads to increased expression of the onco protein, is a well-known mechanism in the genesis of B-cell lymphomas. In contrast, the role of gene amplification in activation of oncogene s in non-Hodgkin's lymphomas is poorly characterized. To study the BCL 2 amplification we performed comparative genomic hybridization (CGH), Southern blot hybridization, Western analysis, immunohistochemistry, m etaphase fluorescence in situ hybridization, and chromosome analysis o n 26 cases of diffuse large B-cell lymphoma (large noncleaved cell lym phoma). The gain or high-level amplification of 18q was found in eight tumors (31%) by CGH, and Southern analysis revealed BCL2 amplificatio n in these cases, but not in the cases with normal chromosome 18 or t( 14;18)(q32;q21). Western immunoblot analysis and immunohistochemistry revealed a high-level expression of BCL2 protein in the cases with BCL 2 amplification and t(14;18)(q32;q21). However, translocation (14;18)( q32;q21) was not detected in any of the cases with BCL2 amplification. Therefore, our results suggest that amplification of the BCL2 gene is an important mechanism for BCL2 protein overexpression in diffuse lar ge B-cell lymphoma. (C) 1997 by The American Society of Hematology.