Integrative Analysis of Somatic Mutations Altering MicroRNA Targeting in Cancer Genomes

Jesse D. Ziebarth, Anindya Bhattacharya, Yan Cui

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Determining the functional impact of somatic mutations is crucial to understanding tumorigenesis and metastasis. Recent sequences of several cancers have provided comprehensive lists of somatic mutations across entire genomes, enabling investigation of the functional impact of somatic mutations in non-coding regions. Here, we study somatic mutations in 3′UTRs of genes that have been identified in four cancers and computationally predict how they may alter miRNA targeting, potentially resulting in dysregulation of the expression of the genes harboring these mutations. We find that somatic mutations create or disrupt putative miRNA target sites in the 3′UTRs of many genes, including several genes, such as MITF, EPHA3, TAL1, SCG3, and GSDMA, which have been previously associated with cancer. We also integrate the somatic mutations with germline mutations and results of association studies. Specifically, we identify putative miRNA target sites in the 3′UTRs of BMPR1B, KLK3, and SPRY4 that are disrupted by both somatic and germline mutations and, also, are in linkage disequilibrium blocks with high scoring markers from cancer association studies. The somatic mutation in BMPR1B is located in a target site of miR-125b; germline mutations in this target site have previously been both shown to disrupt regulation of BMPR1B by miR-125b and linked with cancer.

Original languageEnglish (US)
Article numbere47137
JournalPloS one
Volume7
Issue number10
DOIs
StatePublished - Oct 16 2012

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somatic mutation
MicroRNAs
microRNA
Genes
Genome
Mutation
neoplasms
genome
Germ-Line Mutation
Neoplasms
mutation
germ cells
genes
linkage disequilibrium
Linkage Disequilibrium
metastasis
carcinogenesis
Carcinogenesis
gene expression
Neoplasm Metastasis

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Integrative Analysis of Somatic Mutations Altering MicroRNA Targeting in Cancer Genomes. / Ziebarth, Jesse D.; Bhattacharya, Anindya; Cui, Yan.

In: PloS one, Vol. 7, No. 10, e47137, 16.10.2012.

Research output: Contribution to journalArticle

Ziebarth, Jesse D. ; Bhattacharya, Anindya ; Cui, Yan. / Integrative Analysis of Somatic Mutations Altering MicroRNA Targeting in Cancer Genomes. In: PloS one. 2012 ; Vol. 7, No. 10.
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