Differential Allele-Specific Expression Uncovers Breast Cancer Genes Dysregulated by Cis Noncoding Mutations.

TitleDifferential Allele-Specific Expression Uncovers Breast Cancer Genes Dysregulated by Cis Noncoding Mutations.
Publication TypeJournal Article
Year of Publication2020
AuthorsPrzytycki, PF, Singh, M
JournalCell Syst
Volume10
Issue2
Pagination193-203.e4
Date Published2020 02 26
ISSN2405-4720
Abstract

<p>Identifying cancer-relevant mutations in noncoding regions is challenging due to the large numbers of such mutations, their low levels of recurrence, and difficulties in interpreting their functional impact. To uncover genes that are dysregulated due to somatic mutations in cis, we build upon the concept of differential allele-specific expression (ASE) and introduce methods to identify genes within an individual's cancer whose ASE differs from what is found in matched normal tissue. When applied to breast cancer tumor samples, our methods detect the known allele-specific effects of copy number variation and nonsense-mediated decay. Further, genes that are found to recurrently exhibit differential ASE across samples are cancer relevant. Genes with cis mutations are enriched for differential ASE, and we find 147 potentially functional noncoding mutations cis to genes that exhibit significant differential ASE. We conclude that differential ASE is a promising means for discovering gene dysregulation due to cis noncoding mutations.</p>

DOI10.1016/j.cels.2020.01.002
Alternate JournalCell Syst
PubMed ID32078798
PubMed Central IDPMC7457951
Grant ListR01 CA208148 / CA / NCI NIH HHS / United States
R01 GM076275 / GM / NIGMS NIH HHS / United States