| Literature DB >> 24185510 |
Dan R Robinson1, Yi-Mi Wu, Pankaj Vats, Fengyun Su, Robert J Lonigro, Xuhong Cao, Shanker Kalyana-Sundaram, Rui Wang, Yu Ning, Lynda Hodges, Amy Gursky, Javed Siddiqui, Scott A Tomlins, Sameek Roychowdhury, Kenneth J Pienta, Scott Y Kim, J Scott Roberts, James M Rae, Catherine H Van Poznak, Daniel F Hayes, Rashmi Chugh, Lakshmi P Kunju, Moshe Talpaz, Anne F Schott, Arul M Chinnaiyan.
Abstract
Breast cancer is the most prevalent cancer in women, and over two-thirds of cases express estrogen receptor-α (ER-α, encoded by ESR1). Through a prospective clinical sequencing program for advanced cancers, we enrolled 11 patients with ER-positive metastatic breast cancer. Whole-exome and transcriptome analysis showed that six cases harbored mutations of ESR1 affecting its ligand-binding domain (LBD), all of whom had been treated with anti-estrogens and estrogen deprivation therapies. A survey of The Cancer Genome Atlas (TCGA) identified four endometrial cancers with similar mutations of ESR1. The five new LBD-localized ESR1 mutations identified here (encoding p.Leu536Gln, p.Tyr537Ser, p.Tyr537Cys, p.Tyr537Asn and p.Asp538Gly) were shown to result in constitutive activity and continued responsiveness to anti-estrogen therapies in vitro. Taken together, these studies suggest that activating mutations in ESR1 are a key mechanism in acquired endocrine resistance in breast cancer therapy.Entities:
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Year: 2013 PMID： 24185510 PMCID： PMC4009946 DOI： 10.1038/ng.2823
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330