VH mutation status and VDJ rearrangement structure in mantle cell lymphoma:: correlation with genomic aberrations, clinical characteristics, and outcome

Immunoglobulin variable heavy chain gene (V-H) mutation status and VDJ rearrangement structure were analyzed in 141 patients with mantle cell lymphoma (MCL) and correlated with biologic and clinical characteristics; 29% of the MCLs displayed mutated V-H using a 98% germline homology cutoff. Striking differences occurred in the VH mutation subgroups with respect to the use of specific V genes. Rearrangements involving V4-34 and V3-21 were almost exclusively unmutated, whereas rearrangements using V4-59 and V3-23 were typically mutated. Significant association occurred between mutated V-H with shorter CDR3 lengths and the use of J(H)4b. V3-21 and V4-59 were involved in highly characteristic rearrangements, implying that antigen specificity might have been involved in MCL development. There was no evidence for isotype switch recombination or Bcl-6 expression in any MCL. ZAP70 expression was not different in V-H-mutated or unmutated MCL. Although the deletions 11q- and 17p- showed a balanced distribution, an overrepresentation was observed for trisomies +3q, +8q, and tetraploidy in the V-H-unmutated subgroup and +12q in the V-H-mutated subgroup. Clinically, mutated V-H was associated with a higher rate of complete remission, but there was no correlation between VH mutation status and other clinical characteristics or overall survival. (Blood. 2003; 102:3003-3009) (C) 2003 by The American Society of Hematology.