Keywords

Genome sequencing, RNA-motif, Human Tumors, Noncoding Mutation

Abstract

A major challenge in cancer research is to determine the biological and clinical significance of somatic mutations in noncoding regions. This has been studied in terms of recurrence, functional impact, and association to individual regulatory sites, but the combinatorial contribution of mutations to common RNA regulatory motifs has not been explored. Therefore, we developed a new method, MIRA (mutation identification for RNA alterations), to perform an unbiased and comprehensive study of significantly mutated regions (SMR) affecting binding sites for RNA-binding proteins (RBP) in cancer. Extracting signals related to RNA-related selection processes and using RNA sequencing (RNA-seq) data from the same specimens, we identified alterations in RNA expression and splicing linked to mutations on RBP binding sites. We found SRSF10 and MBNL1 motifs in introns, HNRPLL motifs at 5′ UTRs, as well as 5′ and 3′ splice-site motifs, among others, with specific mutational patterns that disrupt the motif and impact RNA processing. MIRA facilitates the integrative analysis of multiple genome sites that operate collectively through common RBPs and aids in the interpretation of noncoding variants in cancer.

Original Publication Citation

Singh B, Trincado JL, Tatlow PJ, Piccolo SR, and Eyras E. Genome sequencing and RNAmotif analysis reveal novel damaging non-coding mutations in human tumors. Molecular Cancer Research, March 28, 2018

Document Type

Peer-Reviewed Article

Publication Date

2018-07-01

Publisher

American Association for Cancer Research

Language

English

College

Life Sciences

Department

Biology

University Standing at Time of Publication

Associate Professor

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