title: Variable heavy-chain gene analysis of follicular lymphomas: subclone selection rather than clonal evolution over time.
abstract: To investigate B-cell receptor evolution in follicular lymphomas (FLs), immunoglobulin variable heavy chain (V(H)) gene regions of 3 FLs were analyzed at different time points. One FL with a high somatic mutation load and intraclonal V(H) gene diversity was investigated in situ. V(H) gene transcripts were amplified and sequenced from samples of approximately 50 tumor cells isolated from frozen tissue sections by laser microdissection. Interestingly, the mutation pattern of the prevalent subclone in the relapse biopsy was virtually identical to that of a subclone isolated by microdissection from the presentation biopsy 9 years earlier. In a second FL, proof was obtained that the subclone that dominated the relapse sample had already been present in the initial biopsy. The finding that subclones found in the relapses of these FLs had not evolved over time but were preexistent, challenges the concept of antigen-driven B-cell receptor evolution during disease course.
authors: Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands.
authors: W M
authors: WM
authors: Aarts
authors: R J
authors: RJ
authors: Bende
authors: J G
authors: JG
authors: Bossenbroek
authors: S T
authors: ST
authors: Pals
authors: C J
authors: CJ
authors: van Noesel
mesh_terms: D002471:Cell Transformation, Neoplastic; D002999:Clone Cells; D005629:Frozen Sections; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008224:Lymphoma, Follicular / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D011947:Receptors, Antigen, B-Cell / Q000235:genetics; D013997:Time Factors
chemical_list: D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D011947:Receptors, Antigen, B-Cell