Unknown

Dataset Information

0

Activating ESR1 mutations in hormone-resistant metastatic breast cancer.

ABSTRACT: Breast cancer is the most prevalent cancer in women, and over two-thirds of cases express estrogen receptor-? (ER-?, 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.

SUBMITTER: Robinson DR 

PROVIDER: S-EPMC4009946 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

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 o  ...[more]

Similar Datasets

Unknown ESR1 ligand-binding domain mutations in hormone-resistant breast cancer.
| S-EPMC3903423 | biostudies-literature
Unknown Mutual exclusivity of ESR1 and TP53 mutations in endocrine resistant metastatic breast cancer.
| S-EPMC9090919 | biostudies-literature
Unknown <i>ESR1</i> mutations in metastatic lobular breast cancer patients.
| S-EPMC6384916 | biostudies-literature
Unknown ESR1 Mutations in Circulating Plasma Tumor DNA from Metastatic Breast Cancer Patients.
| S-EPMC4993201 | biostudies-literature
Unknown The Impact of ESR1 Mutations on the Treatment of Metastatic Breast Cancer.
| S-EPMC9680193 | biostudies-literature
Unknown ESR1 mutation as an emerging clinical biomarker in metastatic hormone receptor-positive breast cancer.
| S-EPMC8365900 | biostudies-literature
Unknown ESR1 mutations and therapeutic resistance in metastatic breast cancer: progress and remaining challenges.
| S-EPMC8770568 | biostudies-literature
Unknown Molecular characterisation of aromatase inhibitor-resistant advanced breast cancer: the phenotypic effect of ESR1 mutations.
| S-EPMC6342946 | biostudies-literature
Unknown Heterogeneity and clinical significance of ESR1 mutations in ER-positive metastatic breast cancer patients receiving fulvestrant.
| S-EPMC4869259 | biostudies-literature
Unknown Comparison of ESR1 Mutations in Tumor Tissue and Matched Plasma Samples from Metastatic Breast Cancer Patients.
| S-EPMC5538967 | biostudies-literature