Mantle cell lymphomas with clonal immunoglobulin VH3-21 gene rearrangements exhibit fewer genomic imbalances than mantle cell lymphomas utilizing other immunoglobulin VH genes

A preferential use of one particular immunoglobulin variable heavy chain gene, V(H)3 - 21, has recently been reported in mantle cell lymphoma, where almost all of these V(H)3 - 21(+) mantle cell lymphomas showed usage of the same light chain V-lambda gene ( V-lambda 3 - 19) and also had a tendency towards improved prognosis. These findings suggested that V(H)3 - 21(+) mantle cell lymphomas constitute a distinct subgroup, possibly with antigen stimulation involved in disease pathogenesis. In this study, we applied the comparative genomic hybridization ( CGH) method on 37 mantle cell lymphoma tumors in order to investigate if the V(H)3 - 21(+) tumors are different at the genomic level. Interestingly, V(H)3 - 21(+) mantle cell lymphomas ( n = 14) showed significantly fewer genomic aberrations ( mean 2.4) compared to non- V(H)3 - 21 mantle cell lymphomas ( n = 23) ( mean 4.9). The chromosomal aberrations identified in our study were generally in accordance with previous CGH studies of mantle cell lymphoma; the most frequent aberration was complete or partial loss of chromosome 13, followed by recurrent losses within 6q, 9p, 9q and 11q and frequent gains in 3q, 7p, 8q and 15q. Deletions within 8p and 9p as well as gains in 7p and 15q were found exclusively in the non- V(H)3 - 21(+) utilizing tumors. In summary, V(H)3 - 21(+) mantle cell lymphomas demonstrated both a lower number and a different spectrum of genomic aberrations than mantle cell lymphoma in general, thus supporting the hypothesis that V(H)3 - 21(+) mantle cell lymphomas constitute a new subgroup. The findings presented in this report may explain the tendency for a better clinical outcome for patients whose tumors utilize V(H)3 - 21.