MOLECULAR HETEROGENEITY OF B-LINEAGE DIFFUSE LARGE-CELL LYMPHOMA

B-lineage diffuse large cell lymphoma (B-DLCL) arising de novo is char acterized by a marked degree of clinical heterogeneity. To determine w hether or not the clinical heterogeneity of de novo B-DLCL is reflecte d by heterogeneity in the molecular features of these tumors, we inves tigated the pattern of distribution of several genetic lesions in 70 c ases of de novo B-DLCL at diagnosis. The panel of genetic lesions test ed comprised the molecular alterations most frequently detected in B-D LCL, including rearrangements of BCL2, BCL6, and MYC as well as deleti ons of 6q and mutations of TP53. One or more genetic lesions were dete cted in 39/70 cases of B-DLCL Isolated structural alterations of BCL2, BCL6, 6q or TP53 were detected in 8/70, 10/70, 11/70, and 3/70 cases, respectively. No isolated MYC lesions were detected. Six cases carrie d different combinations of two genetic lesions, including lesions of BCL2 + BCL6 (1 case), BCL2 + MYC (1 case), BCL2 + 6q (2 cases), or BCL 6 + 6q (2 cases). One case had accumulated three genetic lesions, name ly a rearrangement of BCL2 and BCL6 and a mutation of TP53. Overall, t hese data show that multiple distinct patterns of genetic lesions may associate with de novo B-DLCL, indicating that the molecular pathogene sis of this group of lymphomas is characterized by a high degree of mo lecular heterogeneity. (C) 1996 Wiley-Liss, Inc