2018
DOI: 10.1016/j.celrep.2018.07.009
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Functional Annotation of ESR1 Gene Fusions in Estrogen Receptor-Positive Breast Cancer

Abstract: SUMMARYRNA sequencing (RNA-seq) detects estrogen receptor alpha gene (ESR1) fusion transcripts in estrogen receptor-positive (ER+) breast cancer, but their role in disease pathogenesis remains unclear. We examined multiple ESR1 fusions and found that two, both identified in advanced endocrine treatment-resistant disease, encoded stable and functional fusion proteins. In both examples, ESR1-e6>YAP1 and ESR1-e6>PCDH11X, ESR1 exons 1–6 were fused in frame to C-terminal sequences from the partner gene. Functional … Show more

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Cited by 91 publications
(134 citation statements)
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“…HER2, have been well established as drivers of acquired resistance in preclinical studies and in clinical data from patient tumors [ 4 ]. More recently, ESR1 gene fusions were also identified as drivers of acquired resistance in patients with metastatic ER+ breast cancer [ 5 , 6 ]. These combined insights into the underlying biology of acquired endocrine treatment resistance in as many as 40% of resistant patients has resulted in potentially more effective anti-estrogens that are currently being tested in clinical trials.…”
Section: New Class Of Drivers Of Endocrine Treatment Resistance: Singmentioning
confidence: 99%
“…HER2, have been well established as drivers of acquired resistance in preclinical studies and in clinical data from patient tumors [ 4 ]. More recently, ESR1 gene fusions were also identified as drivers of acquired resistance in patients with metastatic ER+ breast cancer [ 5 , 6 ]. These combined insights into the underlying biology of acquired endocrine treatment resistance in as many as 40% of resistant patients has resulted in potentially more effective anti-estrogens that are currently being tested in clinical trials.…”
Section: New Class Of Drivers Of Endocrine Treatment Resistance: Singmentioning
confidence: 99%
“…When introduced into breast cancer cells, ESR1-CCDC170 proteins enhance ligand-independent growth factor signaling, leading to increased cell aggressiveness and tumorigenesis [13]. To date, ESR1-CCDC170 remains the most frequent gene fusion detected in luminal B breast cancer, and its recurrence has been subsequently supported by several recent studies [5,[16][17][18][19]. In addition, this fusion is also detected as a recurrent event in ovarian cancer, and its presence has been associated with exceptional short-term survival [20].…”
mentioning
confidence: 97%
“…We (18) and others (17,64) have recently identified ESR1 gene fusions in MBC, with fusions generally maintaining the DNA binding and N-terminal transcriptional activation domains, but deleting the ligand-binding domain. We recently described a copyshift algorithm that determines imbalance in DNA CN of exons that are 5 0 or 3 0 to the break (18).…”
Section: Discussionmentioning
confidence: 87%