Identification and characterization of BCL6 translocation partner genes inprimary gastric high-grade B-cell lymphoma: Heat shock protein 89 alpha isa novel fusion partner gene of BCL6

Primary gastric high-grade B-cell lymphoma (HGBL) is a special type of non- Hodgkin's lymphoma. So far, the genetic features of this tumor have not bee n well characterized. Recently, a high incidence of BCL6 rearrangements has been detected in HGBL. However, no previous cytogenetic studies have found translocations involving the BCL6 locus (3q27) in HGBL, and the genetic ba sis underlying the BCL6 rearrangements in this tumor remains unclear. We th erefore characterized the partner genes of BCL6 in five primary gastric HGB Ls with a rearranged BCL6 gene by analyzing BCL6 transcripts using the 5' R ACE (rapid amplification of cDNA end) strategy. BCL6 translocation partner genes were identified at the 5' end of the chimeric transcripts in all five cases, including the immunoglobulin heavy-chain (IGH) gene in three cases and the immunoglobulin X-light-chain gene and the heat shock protein 89 alp ha (HSP89A) gene in the other two cases. The chimeric transcripts in all ca ses contained the intact BCL6 exon 2, but lacked exon I, which was replaced by sequences from the partner genes, suggesting that BCL6 expression was u nder the control of regulatory sequences of the partner genes. These result s, for the first time, indicate that immunoglobulin genes, especially IGH, are the most common BCL6 translocation partner genes in primary gastric HGB L and that HSP89A is a novel partner of BCL6. Because immunoglobulin genes are also the most frequent partners of BCL6 in nodal diffuse large B-cell l ymphoma (DLBCL), these data suggest that primary gastric HGBL shares a comm on genetic basis with nodal DLBCL. Genes Chromosomes Cancer 27:69-75, 2000. (C) 2000 Wiley-Liss, inc.