Common-variable immunodeficiency-related lymphomas associate with mutations and rearrangements of BCL-6: pathogenetic and histogenetic implications.
Common-variable immunodeficiency (CVI) patients develop non-Hodgkin's lymphomas (NHL), mainly B-lineage diffuse large-cell lymphomas (DLCL), with a high relative risk. The molecular pathogenesis of CVI-related NHL (CVI-NHL) is unknown. Here we aimed at providing a detailed molecular characterization of CVI-NHL. Rearrangements of BCL-6 were detected in two thirds of CVI-NHL cases examined. All 3 CVI-NHL also harbored point mutations of the BCL-6 5' noncoding regions, which constitute a marker of B-cell transit through the germinal center (GC). The number and molecular pattern of BCL-6 mutations in CVI-NHL were similar to that detected in DLCL of immunocompetent hosts and in DLCL arising in other immunodeficiency settings. Microsatellite instability occurred in one CVI-NHL devoid of a BCL-6 rearrangement. All CVI-NHL scored negative for genetic lesions of BCL-2, p53, c-MYC, REL as well as for viral infection by EBV and HHV-8. Overall, these data indicate that: similarly to other immunodeficiency-related NHL, involvement of BCL6 occurs frequently also in CVI-NHL; and because BCL-6 mutations are acquired by B cells during GC transit, their occurrence in CVI-NHL suggest that these lymphomas are histogenetically related to GC B cells.
Department of Medical Sciences, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy.
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Ariatti
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Migliazza
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Savinelli
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D000328:Adult; D017074:Common Variable Immunodeficiency / Q000150:complications*; D004268:DNA-Binding Proteins / Q000235:genetics*; D015321:Gene Rearrangement; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000150:complications / Q000235:genetics* / Q000473:pathology*; D008297:Male; D018895:Microsatellite Repeats; D009154:Mutation; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors