Recurrent and functional regulatory mutations in breast cancer Journal Article


Authors: Rheinbay, E.; Parasuraman, P.; Grimsby, J.; Tiao, G.; Engreitz, J. M.; Kim, J.; Lawrence, M. S.; Taylor-Weiner, A.; Rodriguez-Cuevas, S.; Rosenberg, M.; Hess, J.; Stewart, C.; Maruvka, Y. E.; Stojanov, P.; Cortes, M. L.; Seepo, S.; Cibulskis, C.; Tracy, A.; Pugh, T. J.; Lee, J.; Zheng, Z.; Ellisen, L. W.; Iafrate, A. J.; Boehm, J. S.; Gabriel, S. B.; Meyerson, M.; Golub, T. R.; Baselga, J.; Hidalgo-Miranda, A.; Shioda, T.; Bernards, A.; Lander, E. S.; Getz, G.
Article Title: Recurrent and functional regulatory mutations in breast cancer
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.
Journal Title: Nature
Volume: 547
Issue: 7661
ISSN: 0028-0836
Publisher: Nature Publishing Group  
Date Published: 2017-07-06
Start Page: 55
End Page: 60
Language: English
DOI: 10.1038/nature22992
PROVIDER: scopus
PUBMED: 28658208
PMCID: PMC5563978
DOI/URL:
Notes: Article -- Export Date: 2 August 2017 -- Source: Scopus
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  1. Jose T Baselga
    484 Baselga