Functional consequence of the MET-T1010I polymorphism in breast cancer.

Shuying Liu, Funda Meric-Bernstam, Napa Parinyanitikul, Bailiang Wang, Agda K Eterovic, Xiaofeng Zheng, Mihai Gagea, Mariana Chavez-MacGregor, Naoto T Ueno, Xiudong Lei, Wanding Zhou, Lakshmy Nair, Debu Tripathy, Powel H Brown, Gabriel N Hortobagyi, Ken Chen, John Mendelsohn, Gordon B Mills, Ana M Gonzalez-Angulo

Index: Oncotarget 6(5) , 2604-14, (2015)

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Abstract

Major breast cancer predisposition genes, only account for approximately 30% of high-risk breast cancer families and only explain 15% of breast cancer familial relative risk. The HGF growth factor receptor MET is potentially functionally altered due to an uncommon germline single nucleotide polymorphism (SNP), MET-T1010I, in many cancer lineages including breast cancer where the MET-T1010I SNP is present in 2% of patients with metastatic breast cancer. Expression of MET-T1010I in the context of mammary epithelium increases colony formation, cell migration and invasion in-vitro and tumor growth and invasion in-vivo. A selective effect of MET-T1010I as compared to wild type MET on cell invasion both in-vitro and in-vivo suggests that the MET-T1010I SNP may alter tumor pathophysiology and should be considered as a potential biomarker when implementing MET targeted clinical trials.