Cellular mesenchymal epithelial transition (C-MET) gene copy number variation in gastric adenocarcinoma: A pilot search for new marker for targeted therapy in HER-2/neu resistance

Indian J Pathol Microbiol. 2020 Jan-Mar;63(1):86-89. doi: 10.4103/IJPM.IJPM_396_19.

Abstract

Increasing HER-2/neu resistance in gastric carcinoma has encouraged search for new biomarkers for targeted therapy. Cellular mesenchymal epithelial transition (C-MET) is one such tyrosine kinase inhibitor proposed for personalized salvage treatment. We determined frequency of C-MET gene copy number variation (CNV) by Fluorescent in-situ hybridization (FISH) in gastric adenocarcinoma (GAC) and sought its correlation with conventional clinicopathologic parameters. Dual-coloured FISH was done on 32 GAC cases. C-MET gene and centromere 7 signals were counted under fluorescent microscope and ratio was calculated for each case. Correlation between C-MET CNV and conventional clinic-pathologic parameters was done by Fischer exact test. CNV was identified in the form of amplification and polysomy (3.1% each) and associated with poorer prognostic parameters. Our pilot study highlights limited subset of patients that may benefit from anti-C-MET-targeted therapy and thus could be a novel biomarker for targeted intervention in GAC.

Keywords: Cellular mesenchymal epithelial transition; HER-2/neu; copy number variation; fluorescent in-situ hybridization; gastric adenocarcinoma.

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / therapy*
  • Adult
  • Aged
  • Biomarkers, Tumor / genetics
  • DNA Copy Number Variations
  • Female
  • Gene Dosage*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Male
  • Middle Aged
  • Pilot Projects
  • Proto-Oncogene Proteins c-met / genetics*
  • Receptor, ErbB-2 / genetics
  • Stomach Neoplasms / genetics*
  • Young Adult

Substances

  • Biomarkers, Tumor
  • ERBB2 protein, human
  • Proto-Oncogene Proteins c-met
  • Receptor, ErbB-2