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Oncotarget. 2015 Feb 20;6(5):2604-14.

Functional consequence of the MET-T1010I polymorphism in breast cancer.

Author information

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.

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.

PMID:
25605252
PMCID:
PMC4413604
DOI:
10.18632/oncotarget.3094
[Indexed for MEDLINE]
Free PMC Article

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