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

Reiner Siebert and colleagues report whole-genome, whole-exome and transcriptome sequencing of Burkitt lymphomas. They identify recurrent mutations in several genes not previously known to be mutated in Burkitt lymphoma, including ID3 , FBXO11 , DDX3X and RHOA . Burkitt lymphoma is a mature aggressive B-cell lymphoma derived from germinal center B cells 1 . 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 2 . Consequently, MYC is deregulated, resulting in massive perturbation of gene expression 3 . 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 4 . 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.