title: Functional consequence of the MET-T1010I polymorphism in breast cancer.
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.
authors.affiliation: Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Shuying
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Funda
authors.initials: F
authors.lastname: Meric-Bernstam
authors.affiliation: Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Napa
authors.initials: N
authors.lastname: Parinyanitikul
authors.affiliation: Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Bailiang
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Agda K
authors.initials: AK
authors.lastname: Eterovic
authors.affiliation: Department of Bioinformatics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Veterinary Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Mihai
authors.initials: M
authors.lastname: Gagea
authors.affiliation: Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Mariana
authors.initials: M
authors.lastname: Chavez-MacGregor
authors.affiliation: Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|Section of Breast Cancer Translational Research, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Naoto T
authors.initials: NT
authors.lastname: Ueno
authors.affiliation: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Xiudong
authors.initials: X
authors.lastname: Lei
authors.affiliation: Department of Bioinformatics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Wanding
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Lakshmy
authors.initials: L
authors.lastname: Nair
authors.affiliation: Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Debu
authors.initials: D
authors.lastname: Tripathy
authors.affiliation: Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Powel H
authors.initials: PH
authors.lastname: Brown
authors.affiliation: Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Hortobagyi
authors.affiliation: Department of Bioinformatics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Ken
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: John
authors.initials: J
authors.lastname: Mendelsohn
authors.affiliation: Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Gordon B
authors.initials: GB
authors.lastname: Mills
authors.affiliation: Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Gonzalez-Angulo
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D053208:Kaplan-Meier Estimate; D016513:Mice, SCID; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met