Molecular heterogeneity in MCL defined by the use of specific VH genes and the frequency of somatic mutations

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Abstract
This study explores whether the presence of somatic mutations or a biased use of IgV H genes were associated with the clinical features in a series of 96 patients with mantle cell lymphoma (MCL). The cases were studied by seminested polymerase chain reaction using primers from the FR1 and JHregions. There was an unexpectedly high frequency of somatic mutations, with 29 of 103 sequences showing more than 2% of mutations. Biased usage of specific V H segments was also found; the most widely used genes in this series wereVH3-21 (10 cases),VH3-23 (9 cases),VH4-34 (11 cases), andVH4-59 (9 cases).V H mutation frequency, taking into account different thresholds, did not distinguish different overall survival probabilities. Nevertheless, a more frequent use ofVH3-21 or VH4-59 (8 of 18) was observed in the group of long-term survivors (18 cases > 5 years; P < .01). None of these long-term survivors presented the VH3-23 gene rearrangement. As in other lymphoproliferative disorders, the expression of CD38 or p53 or both was associated with a poorer survival probability. This nonrandom usage of IgVH segments suggests that specific antigens may play a pathogenically relevant role in the genesis or progression of subsets of MCL cases and may help in distinguishing a significant group of MCL long-term survivors.

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