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Functional consequence of the MET-T 1010I polymorphism in breast cancer

2014; Impact Journals LLC; Volume: 6; Issue: 5 Linguagem: Inglês

10.18632/oncotarget.3094

1949-2553

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

Fibroblast Growth Factor Research

// Shuying Liu 1,2 , Funda Meric-Bernstam 3 , Napa Parinyanitikul 1 , Bailiang Wang 1 , Agda K. Eterovic 2 , Xiaofeng Zheng 4 , Mihai Gagea 5 , Mariana Chavez-MacGregor 1 , Naoto T. Ueno 1,6 , Xiudong Lei 7 , Wanding Zhou 4 , Lakshmy Nair 1 , Debu Tripathy 1 , Powel H. Brown 8 , Gabriel N. Hortobagyi 1 , Ken Chen 4 , John Mendelsohn 9 , Gordon B. Mills 2 and Ana M. Gonzalez-Angulo 1,2 1 Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 2 Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 3 Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 4 Department of Bioinformatics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 5 Department of Veterinary Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 6 Section of Breast Cancer Translational Research, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 7 Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 8 Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 9 Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Correspondence: Shuying Liu, email: // Keywords : MET mutations, Breast Cancer, Malignant transformation Received : September 09, 2014 Accepted : December 24, 2014 Published : December 31, 2014 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-viv o suggests that the MET- T1010I SNP may alter tumor pathophysiology and should be considered as a potential biomarker when implementing MET targeted clinical trials.