High prevalence of MAP2K1 mutations in variant and IGHV4-34-expressing hairy-cell leukemias

Nat Genet. 2014 Jan;46(1):8-10. doi: 10.1038/ng.2828. Epub 2013 Nov 17.

Abstract

To understand the genetic mechanisms driving variant and IGHV4-34-expressing hairy-cell leukemias, we performed whole-exome sequencing of leukemia samples from ten affected individuals, including six with matched normal samples. We identified activating mutations in the MAP2K1 gene (encoding MEK1) in 5 of these 10 samples and in 10 of 21 samples in a validation set (overall frequency of 15/31), suggesting potential new strategies for treating individuals with these diseases.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Connectin / genetics
  • Gene Rearrangement, B-Lymphocyte, Heavy Chain / genetics*
  • Humans
  • Immunoglobulin Heavy Chains / genetics*
  • Immunoglobulin Variable Region / genetics
  • Leukemia, Hairy Cell / genetics*
  • MAP Kinase Kinase 1 / genetics*
  • Mutation Rate*
  • Nuclear Proteins / genetics
  • Ribonucleoproteins / genetics
  • Splicing Factor U2AF
  • Transcription Factors / genetics
  • Tumor Suppressor Protein p53 / genetics

Substances

  • ARID1A protein, human
  • Connectin
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Variable Region
  • Nuclear Proteins
  • Ribonucleoproteins
  • Splicing Factor U2AF
  • TP53 protein, human
  • TTN protein, human
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • U2AF1 protein, human
  • MAP Kinase Kinase 1
  • MAP2K1 protein, human

Associated data

  • RefSeq/NM_001025203
  • RefSeq/NM_001126114
  • RefSeq/NM_002755
  • RefSeq/NM_003319
  • RefSeq/NM_006015