The genetic variability of the VH genes in follicular lymphoma:: the impact of the hypermutation mechanism

Follicular lymphoma (FL) cells have inherited an activated hypermutation mechanism from their origin of germinal centre B cells. Based on today's knowledge of the intrinsic properties related to this mechanism and the V-H base composition, reconsideration of previous reports should be made on a broader range of samples. The present study examined the mutation pattern of the V-H genes expressed by 55 cases of FL. FL V-H genes showed evidence of antigenic selection in 30% of cases with 88% carrying a functional sig and 78.2% showing intraclonal variation. V-H family and gene segment utilization was found to be roughly similar to that of normal B lymphocytes. FL V-H genes revealed extensive variations. 17% of the V-H exons harboured a total of five deletions, three duplications and two insertions as compared to the most homologous germline counterpart. The V-H genes of one tumour displayed three populations with varying CDR3 length at diagnosis. At relapse, emergence of a differently mutated gene, additional mutations reminiscent of ongoing mutations or no variation was prominent. From this study the heterogeneity of FLs is well established and ongoing mutations are seen in the scope of the activated status of the hypermutation mechanism rather than antigen-stimulated tumour growth.