The Mutational Landscape of Chromatin Regulatory Factors Across 4,623 Tumor Samples

Genome Biol. 2013;14(9):r106. doi: 10.1186/gb-2013-14-9-r106.

Abstract

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 indifferent 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Transformation, Neoplastic / genetics*
  • Cell Transformation, Neoplastic / metabolism
  • Cell Transformation, Neoplastic / pathology
  • Chromatin / chemistry
  • Chromatin / metabolism*
  • Chromatin Assembly and Disassembly
  • E1A-Associated p300 Protein / genetics*
  • E1A-Associated p300 Protein / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Gene Regulatory Networks
  • Histone-Lysine N-Methyltransferase
  • Humans
  • Mutation Rate
  • Myeloid-Lymphoid Leukemia Protein / genetics*
  • Myeloid-Lymphoid Leukemia Protein / metabolism
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Protein Interaction Mapping

Substances

  • Chromatin
  • KMT2A protein, human
  • Myeloid-Lymphoid Leukemia Protein
  • Histone-Lysine N-Methyltransferase
  • E1A-Associated p300 Protein
  • EP300 protein, human