RICTOR gene amplification is correlated with metastasis and therapeutic resistance in triple-negative breast cancer

Said El Shamieh 1Fatima Saleh 1Salim Moussa 1Joseph Kattan 2Fadi Farhat 2 3

Affiliations

1Department of Medical Laboratory Sciences, Faculty of Health Sciences, Beirut Arab University, Beirut, Lebanon.

2Department of Hematology-Oncology, Saint Joseph Faculty of Medicine, Beirut, Lebanon.

3Department of Hematology & Oncology, Hammoud Hospital UMC, Saida, Lebanon.

PMID: 29790419

DOI: 10.2217/pgs-2018-0019

Abstract

Triple-negative breast cancer (TNBC) is characterized by its aggressive behavior, metastasis and lack of targeted therapies. Herein, we discuss the clinical, histopathological and genetic profile of a woman diagnosed with TNBC. Since the patient had no durable response to chemotherapy, a genetic profiling was carried out. Next-generation sequencing analysis of 592 genes showed a missense mutation, p.E545A in PIK3CA, thus the patient was started on the mTOR inhibitor everolimus, in combination with exemestane, which controlled her pain; however, the disease progressed aggressively. More importantly, next-generation sequencing analysis showed a RICTOR gene amplification (eight copies) suggesting that RICTOR promotes the genesis of TNBC. We conclude that determining regulators of RICTOR and furthermore, their inhibitors might decrease cancer cells proliferation rate in patients with TNBC.

Keywords: RICTOR; copy number variations; next generation sequencing; triple-negative breast cancer.