MET exon 14 skipping mutations and gene amplification in a Taiwanese lung cancer population

PLoS One. 2019 Aug 1;14(8):e0220670. doi: 10.1371/journal.pone.0220670. eCollection 2019.

Abstract

Somatic mutations of MET gene are emerging as important driver mutations for lung cancers. To identify the common clinicopathological features of MET exon 14 skipping mutations and amplification and clarify whether the two MET gene alterations cause protein overexpression were investigated using 196 lung cancer samples of Taiwan through real time-qPCR/sequencing, fluorescence in situ hybridization, and immunohistochemistry. The two MET gene alterations are both present in low frequency, ~1%, in the studied lung cancer population of Taiwan. MET exon 14 skipping mutations were identified from two early-stage patients, who were both relatively advanced in age, and did not carry other driver mutations. One was an adenocarcinoma and the other was a rare carcinosarcoma. Three gene amplifications cases were identified. Neither of the two MET gene alterations would lead to protein overexpression; hence, direct detection in nucleic acid level would be a preferred and straightforward solution for the identification of skipping mutations. The presence of MET exon 14 mutations in minor histological types of lung cancers urge to extend screening scope of this mutation in lung cancer and treatment response evaluation in clinical trials. These would be important next steps for the success of MET target therapy in clinical practice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinosarcoma / genetics
  • Exons / genetics*
  • Female
  • Gene Amplification / genetics*
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • In Situ Hybridization, Fluorescence
  • Lung Neoplasms / genetics*
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Proto-Oncogene Proteins c-met / genetics*
  • Real-Time Polymerase Chain Reaction
  • Taiwan

Substances

  • MET protein, human
  • Proto-Oncogene Proteins c-met

Grants and funding

This work was supported by the Chang Gung Memorial Hospital, Chiayi, Taiwan (to YHT, Grant No: CORPG6F0021-3; to JL, Grant No: CMRPG6F0471-3). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.