The genomic landscape of mantle cell lymphoma is related to the epigenetically determined chromatin state of normal B cells
A partir d'échantillons tumoraux prélevés sur 56 patients atteints d'un lymphome à cellules du manteau, cette étude met en évidence diverses mutations somatiques en association avec des anomalies épigénétiques liées à l'état de la chromatine dans les lymphocytes B
In this study, we define the genetic landscape of mantle cell lymphoma through exome sequencing of 56 cases of mantle cell lymphoma. We identified recurrent mutations in ATM, CCND1, MLL2 and TP53. We further identified a number of novel genes recurrently mutated in patients with mantle cell lymphoma including RB1, WHSC1, POT1, and SMARCA4. We noted that mantle cell lymphomas have a distinct mutational profile compared to lymphomas from other B-cell stages. The ENCODE project has defined the chromatin structure of many cell types. However, a similar characterization of primary human mature B cells has been lacking. We defined, for the first time, the chromatin structure of primary human naïve, germinal center and memory B cells through chromatin immunoprecipitation and sequencing (ChIP-seq) for H3K4me1, H3K4me3, H3Ac, H3K36me3, H3K27me3 and PolII). We found that somatic mutations that occur more frequently in either mantle cell lymphomas or Burkitt lymphomas were associated with open chromatin in their respective B cells of origin, naïve B cells and germinal center B cells. Our work thus elucidates the landscape of gene-coding mutations in mantle cell lymphoma and the critical interplay between epigenetic alterations associated with B cell differentiation and the acquisition of somatic mutations in cancer.
Blood 2014