Recurrent mutation of the ID3 gene in Burkitt lymphoma identified by integrated genome, exome and transcriptome sequencing

Nat Genet. 2012 Dec;44(12):1316-20. doi: 10.1038/ng.2469. Epub 2012 Nov 11.

Abstract

Burkitt lymphoma is a mature aggressive B-cell lymphoma derived from germinal center B cells. Its cytogenetic hallmark is the Burkitt translocation t(8;14)(q24;q32) and its variants, which juxtapose the MYC oncogene with one of the three immunoglobulin loci. Consequently, MYC is deregulated, resulting in massive perturbation of gene expression. Nevertheless, MYC deregulation alone seems not to be sufficient to drive Burkitt lymphomagenesis. By whole-genome, whole-exome and transcriptome sequencing of four prototypical Burkitt lymphomas with immunoglobulin gene (IG)-MYC translocation, we identified seven recurrently mutated genes. One of these genes, ID3, mapped to a region of focal homozygous loss in Burkitt lymphoma. In an extended cohort, 36 of 53 molecularly defined Burkitt lymphomas (68%) carried potentially damaging mutations of ID3. These were strongly enriched at somatic hypermutation motifs. Only 6 of 47 other B-cell lymphomas with the IG-MYC translocation (13%) carried ID3 mutations. These findings suggest that cooperation between ID3 inactivation and IG-MYC translocation is a hallmark of Burkitt lymphomagenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Burkitt Lymphoma / genetics*
  • Chromosome Mapping
  • Chromosomes, Human, Pair 14 / genetics
  • Chromosomes, Human, Pair 8 / genetics
  • Cohort Studies
  • Female
  • Genes, Immunoglobulin
  • Genes, myc / genetics
  • Genome, Human
  • Humans
  • Inhibitor of Differentiation Proteins / genetics*
  • Male
  • Molecular Sequence Data
  • Mutation*
  • Neoplasm Proteins / genetics*
  • Sequence Analysis, DNA
  • Somatic Hypermutation, Immunoglobulin
  • Transcriptome / genetics*
  • Translocation, Genetic / genetics

Substances

  • Inhibitor of Differentiation Proteins
  • Neoplasm Proteins
  • ID3 protein, human

Associated data

  • GEO/GSE10172
  • GEO/GSE22470
  • GEO/GSE4475