The mutational landscape of chromatin regulatory factors across 4,623 tumor samples

Background: Chromatin regulatory factors are emerging as important genes in cancer development and are regarded as interesting candidates for novel targets for cancer treatment. However, we lack a comprehensive understanding of the role of this group of genes in different cancer types. Results: We have analyzed 4,623 tumor samples from thirteen anatomical sites to determine which chromatin regulatory factors are candidate drivers in these different sites. We identify 34 chromatin regulatory factors that are likely drivers in tumors from at least one site, all with relatively low mutational frequency. We also analyze the relative importance of mutations in this group of genes for the development of tumorigenesis in each site, and in different tumor types from the same site. Conclusions: We find that, although tumors from all thirteen sites show mutations in likely driver chromatin regulatory factors, these are more prevalent in tumors arising from certain tissues. With the exception of hematopoietic, liver and kidney tumors, as a median, the mutated factors are less than one fifth of all mutated drivers across all sites analyzed. We also show that mutations in two of these genes, MLL and EP300, correlate with broad expression changes across cancer cell lines, thus presenting at least one mechanism through which these mutations could contribute to tumorigenesis in cells of the corresponding tissues.We acknowledge funding from the Spanish Ministry of Economy and Competitivity (grant numbers SAF2009-06954 and SAF2012-36199) and the Spanish National Institute of Bioinformatics. AJ-S is supported by an FPI fellowshi