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