1. Functional consequence of the MET-T 1010I polymorphism in breast cancer
- Author
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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, and Gonzalez-Angulo, Ana M
- Subjects
Genetics ,Prevention ,Cancer ,Breast Cancer ,Aetiology ,2.1 Biological and endogenous factors ,Animals ,Biomarkers ,Tumor ,Breast Neoplasms ,Cell Line ,Tumor ,Cell Movement ,Cell Proliferation ,Female ,Gene Frequency ,Genetic Predisposition to Disease ,Humans ,Kaplan-Meier Estimate ,Mice ,SCID ,Middle Aged ,Neoplasm Invasiveness ,Phenotype ,Polymorphism ,Single Nucleotide ,Prognosis ,Proto-Oncogene Proteins c-met ,Time Factors ,Transfection ,Tumor Burden ,Oncology and Carcinogenesis - 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.
- Published
- 2015