Genetic instability is associated with histological transformation of follicle center lymphoma

Follicle center lymphoma (FCL) is an indolent B cell non-Hodgkin's lymphoma (NHL) characterized genetically by the t(14;18) translocation. Histologica l transformation and clinical progression of FCLs are frequently associated with secondary genetic alterations at both nucleic acid and chromosomal le vels. To determine the type and pattern of genomic instability occurring in histological transformation of FCLs and the role of DNA mismatch repair de fects in this procedure, we have performed microsatellite analysis, compara tive genomic hybridization (CGH) and mutational analysis of hMLH1 and hMSH2 genes on serial biopsy specimens from patients with FCL transformed to dif fuse large cell lymphoma (DLCL). Paired biopsy samples of eight patients we re analyzed for microsatellite instability and structural alterations for h MLH1 and hMSH2 genes, and tumor samples of five patients were subjected to CGH analysis. A high level of microsatellite instability was associated wit h histological transformation of two cases of FCL, but no mutations of the hMLH1 and hMSH2 genes were detected in any of the lymphoma samples. In the five cases subjected to CGH analysis, the histological transformation of FC Ls was associated with genomic imbalances at 21 chromosomal regions. The ge nomic abnormalities found were rather heterogeneous and none of the genetic changes were overrepresented in the transformed DLCLs. These data suggest that histological transformation of FCLs to DLCL is frequently associated w ith genome wide instability at both nucleic acid and chromosomal levels, al though mutations of the hMSH1 and hMLH2 genes are not involved in this proc ess.