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Updated: Feb 7, 2026

Targeted DNA Methylation Analysis by Next-generation Sequencing
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Identification of MET exon14 skipping by targeted DNA- and RNA-based next-generation sequencing in pulmonary

Yan Li1, Lianju Gao2, Di Ma3

  • 1Departments of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Lung Cancer (Amsterdam, Netherlands)
|July 24, 2018
PubMed
Abstract

Insights

MET exon14 skipping mutations are found in 20.8% of pulmonary sarcomatoid carcinomas (PSCs). This mutation is linked to poorer disease-free survival, highlighting the need for clinical screening and targeted MET TKI therapy.

Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • Pulmonary sarcomatoid carcinomas (PSCs) are aggressive non-small cell lung cancers with poor prognosis.
  • MET exon14 skipping (METex14 skipping) represents a potential therapeutic target in PSCs through MET tyrosine kinase inhibitors (TKIs).

Purpose of the Study:

  • To investigate the frequency and clinical significance of MET exon14 skipping in Chinese PSC patients.
  • To evaluate the efficacy of DNA- and RNA-based Next Generation Sequencing (NGS) for detecting METex14 skipping.

Main Methods:

  • Targeted DNA- and RNA-based NGS was employed to analyze MET exon14 alterations in 77 Chinese PSC patients.
  • Demographic features and clinical outcomes of patients with METex14 skipping mutations were analyzed.

Main Results:

  • METex14 skipping was identified in 20.8% of PSCs, with high concordance (96.1%) between DNA- and RNA-based NGS.
  • Thirteen distinct genomic variants were found to induce METex14 skipping.
  • METex14 skipping was associated with older patient age and served as an unfavorable prognostic factor for disease-free survival (DFS).

Conclusions:

  • RNA-based sequencing is recommended for accurate detection of METex14 skipping due to its ability to identify variants affecting splice sites.
  • Clinical screening for METex14 skipping is crucial for identifying PSC patients who could benefit from targeted MET TKI therapy, especially given their poor prognosis.
Keywords:
DNA-based NGSMETexon14 skippingPulmonary sarcomatoid carcinomasRNA-based NGSSurvival

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