Genomic landscape and prognostic analysis of mantle cell lymphoma.

Abstract

To gain insight into the molecular pathogenesis of patients with mantle cell lymphoma (MCL), next-generation whole-exome sequencing of 16 MCL patients was performed. We identified recurrent mutations in genes that are well known to be functionally relevant in MCL, including ATM (37.5%), TP53 (31.3%), WHSC1 (31.3%), CCND1 (18.8%), NOTCH2 (6.3%), and CDKN2A (6.3%). We also identified somatic mutations in genes for which a functional role in MCL has not been previously suspected. These genes included CCDC15, APC, CDH1, S1PR1, ATRX, BRCA2, CASP8, and NOTCH3. Further, we investigated the prognostic factors associated with MCL from clinical, pathological, and genetic mutations. Mutations of TP53 (P = 0.021) was a significant prognostic factor with shorter overall survival (OS). Although there was no statistical difference, the median survival time of patients with WHSC1 mutations was shorter than those without mutations (P = 0.070). Mutations in ATM and CCND1 had no prognostic value (P = 0.552, 0.566). When adjusted for MCL International Prognostic Index (MIPI) or combined MCL-International Prognostic Index (MIPI-c), TP53 and WHSC1 mutations were the most important prognostic factors in MCL (P < 0.05). Our data provide an unbiased view of the landscape of mutations in MCL and commend that all patients benefit from mutations of TP53 and WHSC1 at diagnosis, in addition to MIPI and MIPI-c score.