Recurrent and functional regulatory mutations in breast cancer
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Author(s)
Parasuraman, Prasanna
Tiao, Grace
Kim, Jaegil
Taylor-Weiner, Amaro
Rodriguez-Cuevas, Sergio
Rosenberg, Mara
Hess, Julian
Stewart, Chip
Maruvka, Yosef E.
Stojanov, Petar
Date Issued
June 2017
Journal
Nature
Publisher
Nature Publishing Group
Citation
Rheinbay, Esther et al. “Recurrent and Functional Regulatory Mutations in Breast Cancer.” Nature 547, 7661 (June 2017): 55–60
Version
Author's final manuscript
Abstract
Genomic analysis of tumours has led to the identification of hundreds of cancer genes on the basis of the presence of mutations in protein-coding regions. By contrast, much less is known about cancer-causing mutations in non-coding regions. Here we perform deep sequencing in 360 primary breast cancers and develop computational methods to identify significantly mutated promoters. Clear signals are found in the promoters of three genes. FOXA1, a known driver of hormone-receptor positive breast cancer, harbours a mutational hotspot in its promoter leading to overexpression through increased E2F binding. RMRP and NEAT1, two non-coding RNA genes, carry mutations that affect protein binding to their promoters and alter expression levels. Our study shows that promoter regions harbour recurrent mutations in cancer with functional consequences and that the mutations occur at similar frequencies as in coding regions. Power analyses indicate that more such regions remain to be discovered through deep sequencing of adequately sized cohorts of patients.
MIT Department
Broad Institute of MIT and Harvard
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Biology
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Creative Commons Attribution-Noncommercial-Share Alike
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DOI of Published Version
https://doi.org/10.1038/NATURE22992
