Noncoding somatic and inherited single-nucleotide variants converge to promote ESR1 expression in breast cancer

ABSTRACT: Sustained expression of the estrogen receptor-α (ESR1) drives two-thirds of breast cancer and defines the ESR1-positive subtype. ESR1 engages enhancers upon estrogen stimulation to establish an oncogenic expression program1. Somatic copy number alterations involving the ESR1 gene occur in approximately 1 % of ESR1-positive breast cancers2–5, 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 ESR1 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-nuc

ORGANISM(S): Homo sapiens

SUBMITTER: Mathieu Lupien 

PROVIDER: E-GEOD-74718 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress