Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma

Nature. Volume 476, Issue 7360: p. 298-303, 27 Jul 2011

10.1038/nature10351

Follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) are the two most common non-Hodgkin lymphomas (NHLs). Here we sequenced tumour and matched normal DNA from 13 DLBCL cases and one FL case to identify genes with mutations in B-cell NHL. We analysed RNA-seq data from these and another 113 NHLs to identify genes with candidate mutations, and then re-sequenced tumour and matched normal DNA from these cases to confirm 109 genes with multiple somatic mutations.

Genes with roles in histone modification were frequent targets of somatic mutation. For example, 32% of DLBCL and 89% of FL cases had somatic mutations in MLL2, which encodes a histone methyltransferase, and 11.4% and 13.4% of DLBCL and FL cases, respectively, had mutations in MEF2B, a calcium-regulated gene that cooperates with CREBBP and EP300 in acetylating histones. Our analysis suggests a previously unappreciated disruption of chromatin biology in lymphomagenesis.

Supplemental Data

• GDC Manifests
  • Controlled-Access Data Download Manifest (3 Files)
  • Open-Access Data Download Manifest (6 Files)

• Clinical Data
  • CGCI-NHL Clinical Data

• mRNA
  • CGCI-NHL mRNA-Seq Level 3 Data
  • CGCI-NHL mRNA-Seq Level 3 Data (Controlled)
  • CGCI-NHL mRNA-Seq Metadata

• Whole Exome Sequencing
  • CGCI-NHL WXS Level 3 Data (Controlled)
  • CGCI-NHL WXS Metadata

• Whole Genome Sequencing
  • CGCI-NHL WGS Level 3 Data (Controlled)
  • CGCI-NHL WGS Metadata

• Miscellaneous Files
  • CGCI-NHL Sample Matrix

Additional Resources

• Office of Cancer Genomics (link is external)

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