Expression and mutational analysis of MET in human solid cancers

Patrick C. Ma, Maria S. Tretiakova, Alexander C. MacKinnon, Nithya Ramnath, Candace Johnson, Sascha Dietrich, Tanguy Seiwert, James G. Christensen, Ramasamy Jagadeeswaran, Thomas Krausz, Everett E. Vokes, Aliya N. Husain, Ravi Salgia

Research output: Contribution to journalArticle

221 Scopus citations

Abstract

MET receptor tyrosine kinase and its ligand hepatocyte growth factor (HGF) regulate a variety of cellular functions, many of which can be dysregulated in human cancers. Activated MET signaling can lead to cell motility and scattering, angiogenesis, proliferation, branching morphogenesis, invasion, and eventual metastasis. We performed systematic analysis of the expression of the MET receptor and its ligand HGF in tumor tissue microarrays (TMA) from human solid cancers. Standard immunohistochemistry (IHC) and a computerized automated scoring system were used. DNA sequencing for MET mutations in both nonkinase and kinase domains was also performed. MET was differentially overexpressed in human solid cancers. The ligand HGF was widely expressed in both tumors, primarily intratumoral, and nonmalignant tissues. The MET/HGF likely is functional and may be activated in autocrine fashion in vivo. MET and stem cell factor (SCF) were found to be positively stained in the bronchioalevolar junctions of lung tumors. A number of novel mutations of MET were identified, particularly in the extracellular semaphorin domain and the juxtamembrane domain. MET-HGF pathway can be assayed in TMAs and is often overexpressed in a wide variety of human solid cancers. MET can be activated through overexpression, mutation, or autocrine signaling in malignant cells. Mutations in the nonkinase regions of MET might play an important role in tumorigenesis and tumor progression. METwould be an important therapeutic antitumor target to be inhibited, and in lung cancer, MET may represent a cancer early progenitor cell marker.

Original languageEnglish (US)
Pages (from-to)1025-1037
Number of pages13
JournalGenes Chromosomes and Cancer
Volume47
Issue number12
DOIs
StatePublished - Dec 2008

All Science Journal Classification (ASJC) codes

  • Genetics
  • Cancer Research

Fingerprint Dive into the research topics of 'Expression and mutational analysis of MET in human solid cancers'. Together they form a unique fingerprint.

  • Cite this

    Ma, P. C., Tretiakova, M. S., MacKinnon, A. C., Ramnath, N., Johnson, C., Dietrich, S., Seiwert, T., Christensen, J. G., Jagadeeswaran, R., Krausz, T., Vokes, E. E., Husain, A. N., & Salgia, R. (2008). Expression and mutational analysis of MET in human solid cancers. Genes Chromosomes and Cancer, 47(12), 1025-1037. https://doi.org/10.1002/gcc.20604