title: Retrospective Review of MET Gene Mutations.
abstract: C-MET proto-oncogene is a tyrosine kinase situated on chromosome 7. C-MET and its ligand hepatocyte growth factor/scatter factor (HGF/SF) play a role in proliferation, differentiation and organ development. C-MET genetic aberrations are found associated with driving tumorigenesis. In this retrospective study, we reviewed molecular analysis data gathered from a cancer institute during a two-year period (2010-2012). Upon detection of tumors harboring c-MET mutations, we determined the status of the other mutations tested and evaluated c-MET expression by fluorescent in-situ hybridization (FISH). Our search resulted in identification of 134 c-MET mutations, 44% of which had mutations of at least one of the other genes tested. No c-MET expression aberrancy was detected in this subset by FISH. Survival amongst the patients with surgically resected metastatic colorectal cancers (CRC) was slightly better in those with only a c-MET mutation compared to those with no mutation detected, although the difference was not statistically significant. When c-MET inhibition becomes an integrated part of chemotherapy practice, our observed frequency of co-mutations will be an argument for utilizing c-MET targeted treatment in combination with other targeted drugs and therapeutic strategies. Larger studies can aid to further parse out c-MET prognostic and therapeutic significance.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Maryam
authors.initials: M
authors.lastname: Zenali
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Vermont Medical Center, Burlington, Vermont.
authors.forename: James
authors.initials: J
authors.lastname: deKay
authors.affiliation: Institute of Personalized Cancer Therapy, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Zesheng
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Stanley
authors.initials: S
authors.lastname: Hamilton
authors.affiliation: Department of Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Zhuang
authors.initials: Z
authors.lastname: Zuo
authors.affiliation: Department of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Xinyan
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Pathology, University of New Mexico, Albuquerque, New Mexico.
authors.forename: Rania
authors.initials: R
authors.lastname: Bakkar
authors.affiliation: Institute of Personalized Cancer Therapy, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Gordon
authors.initials: G
authors.lastname: Mills
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Russell
authors.initials: R
authors.lastname: Broaddus
keywords: C-MET; FISH; co-mutations; targeted therapy