Retrospective review of MET gene mutations
Maryam Zenali1,*, James deKay2,*, Zesheng Liu3, Stanley Hamilton1, Zhuang Zuo4, Xinyan Lu5, Rania Bakkar6, Gordon Mills3, Russell Broaddus1
1 Department of Pathology and Laboratory Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas
2 Department of Pathology and Laboratory Medicine, University of Vermont Medical Center, Burlington, Vermont
3 Institute of Personalized Cancer Therapy, University of Texas MD Anderson Cancer Center, Houston, Texas
4 Department of Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas
5 Department of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, Texas
6 Department of Pathology, University of New Mexico, Albuquerque, New Mexico
* These authors have contributed equally to this work
Correspondence:
Maryam Zenali, email:
Keywords: C-MET, co-mutations, FISH, targeted therapy
Received: February 18, 2015 Accepted: May 5, 2015 Published: May 14, 2015
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.
