Recurrent hyperactive ESR1 fusion proteins in endocrine therapy-resistant breast cancer.

ABSTRACT:

Background

Estrogen receptor-positive (ER-positive) metastatic breast cancer is often intractable due to endocrine therapy resistance. Although ESR1 promoter switching events have been associated with endocrine-therapy resistance, recurrent ESR1 fusion proteins have yet to be identified in advanced breast cancer.

Patients and methods

To identify genomic structural rearrangements (REs) including gene fusions in acquired resistance, we undertook a multimodal sequencing effort in three breast cancer patient cohorts: (i) mate-pair and/or RNAseq in 6 patient-matched primary-metastatic tumors and 51 metastases, (ii) high coverage (>500×) comprehensive genomic profiling of 287-395 cancer-related genes across 9542 solid tumors (5216 from metastatic disease), and (iii) ultra-high cov

SUBMITTER: Hartmaier RJ 

PROVIDER: S-EPMC5913625 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature