Prognostic analysis of mantle cell lymphoma genomes

Mantle cell lymphoma is characterized by a t(11;14) chromosomal translocation; however, it alone is insufficient to result in the disease. A number of secondary genetic alterations have been proposed as essential in MCL pathogenesis. Amongst these, numerous copy number altered regions remain ill-defined, both for location and prognostic significance. In this study we examined in detail the genomes of a panel of 52 MCL cases. Relating gene dosage alterations to disease outcome, we found seven loci that correlated with overall survival. A survival model was constructed based on four of these loci (P = 5.87 x 10-6). Using serial analysis of gene expression and quantitative PCR we investigated the expression of genes within these altered regions and determined that CCNI and CCNG2 may be important in MCL pathogenesis (P = 0.0201 and P = 0.0292, respectively). Our findings reinforce the hypothesis that cell cycle deregulation and apoptosis are key factors in MCL pathogenesis. Array CGH, Long-SAGE, and qPCR were utilized to determine regions of the genome that have prognostic significance when altered in copy number in MCL.