6533b850fe1ef96bd12a85e6

RESEARCH PRODUCT

In the literature: February 2017

subject

description

The hallmark of mantle cell lymphoma (MCL) is the t(11;14)(q13,q32) translocation, which leads to the juxtaposition of CCDN1 to the IgH promoter locus, resulting in cyclin D1 overexpression. However, studies from transgenic mouse show that additional secondary genetic events are required for oncogenic transformation. Epigenetic dysregulation is an important mechanism of oncogenesis and tumour progression, but there are only few genome-wide studies of DNA methylome in MCL and mainly focused on promoter regions. In an elegant article published in Cancer Cell , Queiros et al 1 studied the genome-wide methylation profiles of 82 MCL cases using microarray containing approximately 450 000 CPG sites across the genome. They developed a novel computational strategy to isolate tumour DNA methylation changes from normal cells, in a so called ‘in silico purification’. Based on this strategy, the MCL samples were clustered into two groups—C1 and C2, which display similar methylation patterns to normal germinal centre (GC) inexperienced and GC experienced B cells, respectively, indicating a different B-cell origin. Both groups were highly heterogeneous and this also translated into distinct clinical–biological features, as IgVH mutational status, SOX11 expression, nodal presentation and worse survival for C1 patients. To identify tumour-specific alterations (TSA) from their normal counterpart, the authors compared data obtained from the MCL tumour cells with those coming from different B-cell subpopulations, ranging from haematopoietic progenitor cells to plasma cells. They found that 61%–79% of methylation changes CpGs overlapped with those acquired during B-cell differentiation and were enriched for enhancer elements, whereas the rest of 21%–39% were strictly tumour specific. Overall, hypomethylation in MCL in both the B-cell-related …