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

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Date
2019-01
ICR Author
Cornish, Alexander
Law, Philip
Houlston, Richard
Author
Cornish, AJ
Hoang, PH
Dobbins, SE
Law, PJ
Chubb, D
Orlando, G
Houlston, RS
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Type
Journal Article
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Abstract
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 cis -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 cis -regulatory elements targeting CD69 , IGLL5 , and MMP14 , and single nucleotide variants in a cis -regulatory element for TPRG1 We also show the commonality of pathways targeted by coding and noncoding mutations, exemplified by MMP14 , 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.
URI
https://repository.icr.ac.uk/handle/internal/2998
DOI
https://doi.org/10.1182/bloodadvances.2018026419
Collections
  • Genetics and Epidemiology
Subject
Humans
Lymphoma, B-Cell
Genetic Predisposition to Disease
RNA, Untranslated
Computational Biology
Gene Amplification
Gene Expression Regulation, Neoplastic
Mutation
Open Reading Frames
Databases, Genetic
Promoter Regions, Genetic
Genetic Association Studies
DNA Copy Number Variations
Whole Genome Sequencing
Research team
Cancer Genomics
Language
eng
Date accepted
2018-11-24
License start date
2019-01
Citation
Blood advances, 2019, 3 (1), pp. 21 - 32

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