title: Genetic instability is associated with histological transformation of follicle center lymphoma.
abstract: Follicle center lymphoma (FCL) is an indolent B cell non-Hodgkin's lymphoma (NHL) characterized genetically by the t(14;18) translocation. Histological transformation and clinical progression of FCLs are frequently associated with secondary genetic alterations at both nucleic acid and chromosomal levels. To determine the type and pattern of genomic instability occurring in histological transformation of FCLs and the role of DNA mismatch repair defects in this procedure, we have performed microsatellite analysis, comparative genomic hybridization (CGH) and mutational analysis of hMLH1 and hMSH2 genes on serial biopsy specimens from patients with FCL transformed to diffuse large cell lymphoma (DLCL). Paired biopsy samples of eight patients were analyzed for microsatellite instability and structural alterations for hMLH1 and hMSH2 genes, and tumor samples of five patients were subjected to CGH analysis. A high level of microsatellite instability was associated with 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 FCLs was associated with genomic imbalances at 21 chromosomal regions. The genomic 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 with genome wide instability at both nucleic acid and chromosomal levels, although mutations of the hMSH1 and hMLH2 genes are not involved in this process.
authors.affiliation: Department of Pathology, Faculty of Medicine, Pécs University, Hungary.
authors.forename: M
authors.initials: M
authors.lastname: Nagy
authors.forename: M
authors.initials: M
authors.lastname: Balázs
authors.forename: Z
authors.initials: Z
authors.lastname: Adám
authors.forename: Z
authors.initials: Z
authors.lastname: Petkó
authors.forename: B
authors.initials: B
authors.lastname: Tímár
authors.forename: Z
authors.initials: Z
authors.lastname: Szereday
authors.forename: T
authors.initials: T
authors.lastname: László
authors.forename: R A
authors.initials: RA
authors.lastname: Warnke
authors.forename: A
authors.initials: A
authors.lastname: Matolcsy
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D006801:Humans; D008224:Lymphoma, Follicular / Q000235:genetics* / Q000473:pathology*; D018895:Microsatellite Repeats / Q000235:genetics; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins; D009693:Nucleic Acid Hybridization; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011518:Proto-Oncogene Proteins / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein