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

    Research output: Contribution to journalArticle

    15 Scopus citations

    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 invitro 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.

    Original languageEnglish (US)
    Pages (from-to)2604-2614
    Number of pages11
    JournalOncotarget
    Volume6
    Issue number5
    DOIs
    StatePublished - Jan 1 2015

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    Keywords

    • Breast cancer
    • MET mutations
    • Malignant transformation

    ASJC Scopus subject areas

    • Oncology

    Cite this

    Liu, S., Meric-Bernstam, F., Parinyanitikul, N., Wang, B., Eterovic, A. K., Zheng, X., Gagea, M., Chavez-MacGregor, M., Ueno, N. T., Lei, X., Zhou, W., Nair, L., Tripathy, D., Brown, P. H., Hortobagyi, G. N., Chen, K., Mendelsohn, J., Mills, G. B., & Gonzalez-Angulo, A. M. (2015). Functional consequence of the MET-T1010I polymorphism in breast cancer. Oncotarget, 6(5), 2604-2614. https://doi.org/10.18632/oncotarget.3094