Dataset Information

Allele-Specific Chromatin Recruitment and Therapeutic Vulnerabilities of ESR1 Activating Mutations.

ABSTRACT: Estrogen receptor ? (ER) ligand-binding domain (LBD) mutations are found in a substantial number of endocrine treatment-resistant metastatic ER-positive (ER+) breast cancers. We investigated the chromatin recruitment, transcriptional network, and genetic vulnerabilities in breast cancer models harboring the clinically relevant ER mutations. These mutants exhibit both ligand-independent functions that mimic estradiol-bound wild-type ER as well as allele-specific neomorphic properties that promote a pro-metastatic phenotype. Analysis of the genome-wide ER binding sites identified mutant ER unique recruitment mediating the allele-specific transcriptional program. Genetic screens identified genes that are essential for the ligand-independent growth driven by the mutants. These studies provide insights into the mechanism of endocrine therapy resistance engendered by ER mutations and potential therapeutic targets.

SUBMITTER: Jeselsohn R

PROVIDER: S-EPMC5813700 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Allele-Specific Chromatin Recruitment and Therapeutic Vulnerabilities of ESR1 Activating Mutations.

Jeselsohn Rinath R Bergholz Johann S JS Pun Matthew M Cornwell MacIntosh M Liu Weihan W Nardone Agostina A Xiao Tengfei T Li Wei W Qiu Xintao X Buchwalter Gilles G Feiglin Ariel A Abell-Hart Kayley K Fei Teng T Rao Prakash P Long Henry H Kwiatkowski Nicholas N Zhang Tinghu T Gray Nathanael N Melchers Diane D Houtman Rene R Liu X Shirley XS Cohen Ofir O Wagle Nikhil N Winer Eric P EP Zhao Jean J Brown Myles M

Cancer cell 20180201 2

Estrogen receptor α (ER) ligand-binding domain (LBD) mutations are found in a substantial number of endocrine treatment-resistant metastatic ER-positive (ER<sup>+</sup>) breast cancers. We investigated the chromatin recruitment, transcriptional network, and genetic vulnerabilities in breast cancer models harboring the clinically relevant ER mutations. These mutants exhibit both ligand-independent functions that mimic estradiol-bound wild-type ER as well as allele-specific neomorphic properties t ...[more]

PMID: 29438694

Dataset Information

Allele-Specific Chromatin Recruitment and Therapeutic Vulnerabilities of ESR1 Activating Mutations.

Publications

Allele-Specific Chromatin Recruitment and Therapeutic Vulnerabilities of ESR1 Activating Mutations.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Similar Datasets

Activating ESR1 mutations in hormone-resistant metastatic breast cancer.
| S-EPMC4009946 | biostudies-literature

Cohesin mutations alter DNA damage repair and chromatin structure and create therapeutic vulnerabilities in MDS/AML.
| S-EPMC7934867 | biostudies-literature

Activating <i>ESR1</i> Mutations Differentially Affect the Efficacy of ER Antagonists.
| S-EPMC5340622 | biostudies-literature

Allele-specific gene regulation, phenotypes, and therapeutic vulnerabilities in estrogen receptor alpha mutant endometrial cancer
2022-06-17 | GSE205879 | GEO

Steroid Hormone Receptor and Infiltrating Immune Cell Status Reveals Therapeutic Vulnerabilities of <i>ESR1</i>-Mutant Breast Cancer.
| S-EPMC7854521 | biostudies-literature

ATM deficiency confers specific therapeutic vulnerabilities in bladder cancer.
| S-EPMC10664985 | biostudies-literature

Heritable individual-specific and allele-specific chromatin signatures in humans.
| S-EPMC2929018 | biostudies-literature

Detection of Activating Estrogen Receptor Gene (<i>ESR1</i>) Mutations in Single Circulating Tumor Cells.
| S-EPMC5641250 | biostudies-literature

Allele-specific gene regulation, phenotypes, and therapeutic vulnerabilities in estrogen receptor alpha mutant endometrial cancer (RNA-Seq)
2022-06-17 | GSE205878 | GEO

Allele-specific gene regulation, phenotypes, and therapeutic vulnerabilities in estrogen receptor alpha mutant endometrial cancer (ATAC-Seq)
2022-06-17 | GSE205875 | GEO