Journal
NATURE GENETICS
Volume 48, Issue 10, Pages 1260-1266Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.3650
Keywords
-
Categories
Funding
- National Cancer Institute (NCI) at the National Institute of Health (NIH) [R01CA155004]
- Princess Margaret Cancer Foundation
- Canadian Cancer Society [CCSRI702922]
- Susan G. Komen Foundation [CCR15332792]
- Gattuso-Slaight Personalized Cancer Medicine Fund/PMCF
- Ontario Institute for Cancer Research (OICR)
- Canadian Institute of Health Research (CIHR)
- Prostate Cancer Canada (PCC) [RS2014-04]
- Canadian Breast Cancer Foundation (CBCF)
- Knudson
- CIHR
Ask authors/readers for more resources
Sustained expression of the estrogen receptor-alpha (ESR1) drives two-thirds of breast cancer and defines the ESR1-positive subtype. ESR1 engages enhancers upon estrogen stimulation to establish an oncogenic expression program(1). Somatic copy number alterations involving the ESR1 gene occur in approximately 1% of ESR1-positive breast cancers(2-5), suggesting that other mechanisms underlie the persistent expression of ESR1. We report significant enrichment of somatic mutations within the set of regulatory elements (SRE) regulating ESR1 in 7% of ESR1-positive breast cancers. These mutations regulate ESRI expression by modulating transcription factor binding to the DNA. The SRE includes a recurrently mutated enhancer whose activity is also affected by rs9383590, a functional inherited single-nucleotide variant (SNV) that accounts for several breast cancer risk associated loci. Our work highlights the importance of considering the combinatorial activity of regulatory elements as a single unit to delineate the impact of noncoding genetic alterations on single genes in cancer.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available