Functional consequence of the MET-T1010I polymorphism in breast cancer

Oncotarget. 2015 Feb 20;6(5):2604-14. doi: 10.18632/oncotarget.3094.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • 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 / genetics*
  • Proto-Oncogene Proteins c-met / metabolism
  • Time Factors
  • Transfection
  • Tumor Burden

Substances

  • Biomarkers, Tumor
  • MET protein, human
  • Proto-Oncogene Proteins c-met