Diverse noncoding mutations contribute to deregulation of cis-regulatory landscape in pediatric cancers

Bing He, Peng Gao, Yang Yang Ding, Chia Hui Chen, Gregory Chen, Changya Chen, Hannah Kim, Sarah K. Tasian, Stephen P. Hunger, Kai Tan

Research output: Contribution to journalArticlepeer-review

Abstract

Interpreting the function of noncoding mutations in cancer genomes remains a major challenge. Here, we developed a computational framework to identify putative causal noncoding mutations of all classes by joint analysis of mutation and gene expression data. We identified thousands of SNVs/small indels and structural variants as putative causal mutations in five major pediatric cancers. We experimentally validated the oncogenic role of CHD4 overexpression via enhancer hijacking in B-ALL. We observed a general exclusivity of coding and noncoding mutations affecting the same genes and pathways. We showed that integrated mutation profiles can help define novel patient subtypes with different clinical outcomes. Our study introduces a general strategy to systematically identify and characterize the full spectrum of noncoding mutations in cancers.

Original languageEnglish (US)
Article numberaba3064
JournalScience Advances
Volume6
Issue number30
DOIs
StatePublished - Jul 2020

All Science Journal Classification (ASJC) codes

  • General

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