B-lineage diffuse large cell lymphoma (B-DLCL) arising de novo is chatacterized by a marked degree of clinical heterogeneity. To determine whether or not the clinical heterogeneity of de novo B-DLCL is reflected by heterogeneity in the molecular features of these tumors, we investigated the pattern of distribution of several genetic lesions in 70 cases of de novo B-DLCL at diagnosis. The panel of genetic lesions tested comprised the molecular alterations most frequently detected in 8-DLCL including rearrangements of BCU, BCL6. and MYC as well as deletions of 6q and mutations of TP53. One or more genetic lesions were detected in 39/70 cases of B-DLCL Isolated structural alterations of BCU, BCL6, 6q or TP53 were detected in 8/70, l0/70. i 1/70, and 3/70 cases, respectively. No isolated MYC lesions were detected. Six cases carried different combinations of two genetic lesions, including lesions of BCU + BCL6 (I case), BCU + MYC ( I case), BCU + 6q (2 cases), or BCL6 + 6q
(2 cases). One case had accumulated three genetic lesions, namely a rearrangement of BCU and BCL6 and a mutation of TP53.
Overall, these data show that multiple distinct patterns of genetic lesions may associate with de novo B-DLCL, indicating that the molecular pathogenesis of this group of lymphomas is characterized by a high degree of molecular heterogeneity. Genes .
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