Molecular analysis of non-small cell lung cancer using a dual-targeted DNA and RNA comprehensive genomic profiling

Hidenori Kage1, Shinji Kohsaka2, Kenji Tatsuno3

  • 1The Department of Respiratory Medicine, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655, Japan.

PubMed
Abstract

Insights

The Todai OncoPanel effectively identified actionable genomic alterations in non-small cell lung cancer (NSCLC), including druggable targets and potential for sensitive detection of MET exon 14 skipping using its RNA panel.

Area of Science:

  • Genomic Medicine
  • Oncology
  • Molecular Diagnostics

Background:

  • Comprehensive cancer genomic profiling guides treatment decisions.
  • Current tests analyze DNA from tissue or plasma for hundreds of genes.
  • RNA panels detect fusions and exon skipping, complementing DNA analysis.

Purpose of the Study:

  • To evaluate the Todai OncoPanel, a DNA and RNA targeted sequencing panel, for comprehensive genomic profiling of non-small cell lung cancer (NSCLC).
  • To identify actionable genomic alterations and assess the panel's sensitivity for detecting specific mutations like MET exon 14 skipping.

Main Methods:

  • Analyzed 60 NSCLC samples using the Todai OncoPanel (DNA and RNA) between April 2017 and March 2022.
  • Utilized matched tumor/normal pairs for analysis.
  • Downloaded publicly available genomic data from a cancer genomics database for comparison.

Main Results:

  • TP53 loss-of-function mutations (53%) and EGFR/ERBB2 activating mutations (33%/12% in adenocarcinoma) were detected by the DNA panel.
  • The RNA panel identified 11 fusion genes (all in adenocarcinoma) and detected MET exon 14 skipping in 7% of NSCLC samples.
  • A significantly higher prevalence of MET exon 14 splice site mutations was observed in the public database (2%) compared to the study cohort (p=0.039).

Conclusions:

  • The Todai OncoPanel successfully identified numerous druggable targets in NSCLC.
  • The RNA component of the panel demonstrates high sensitivity for detecting MET exon 14 skipping.
  • This comprehensive profiling approach aids in identifying potential therapeutic strategies for NSCLC patients.