Identification of recurrent noncoding mutations in B-cell lymphoma using capture Hi-C.

The identification of driver mutations is fundamental to understanding oncogenesis. Although genes frequently mutated in B-cell lymphoma have been identified, the search for driver mutations has largely focused on the coding genome. Here we report an analysis of the noncoding genome using whole-genome sequencing data from 117 patients with B-cell lymphoma. Using promoter capture Hi-C data in naive B cells, we define -regulatory elements, which represent an enriched subset of the noncoding genome in which to search for driver mutations. Regulatory regions were identified whose mutation significantly alters gene expression, including copy number variation at -regulatory elements targeting , , and , and single nucleotide variants in a -regulatory element for We also show the commonality of pathways targeted by coding and noncoding mutations, exemplified by , which regulates Notch signaling, a pathway important in lymphomagenesis and whose expression is associated with patient survival. This study provides an enhanced understanding of lymphomagenesis and describes the advantages of using chromosome conformation capture to decipher noncoding mutations relevant to cancer biology.