Using interphase FISH, genomic aberrations were demonstrable in 246 of 300 (82%) B-CLL cases with known VH mutation status in our series (10). The incidences of the individual genomic aberrations in the total group and in dependence on the VH mutation status are shown in Table 2. The incidences of genomic aberrations overall and of trisomy 12 in the two VH subgroups were comparable; by contrast, prognostically unfavorable aberrations (11q-, 17p-) occurred almost exclusively in the VH unmutated, and prognostically favorable aberrations (13q-, 13q- single) more frequently in the VH mutated subgroup. This unbalanced distribution of genomic aberrations emphasizes the different biological backgrounds of the B-CLL subgroups with mutated or unmutated VH and could in part explain their different clinical course. On the other hand, about two-thirds of the VH unmutated B-CLL cases show no unfavorable genomic aberrations, which indicates a differential influence of these factors. Comprehensive studies of gene expression in B-CLL based on DNA chip technology indicate that the global gene expression "signature" of VH mutated and unmutated B-CLL is very similar and that only the expression of a small number of genes discriminates between the two groups (138,139).
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