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 journalArticlepeer-review

24 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 - 2015
Externally publishedYes

Keywords

  • Breast cancer
  • MET mutations
  • Malignant transformation

ASJC Scopus subject areas

  • Oncology

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