Deep targeted sequencing analysis of hot spot mutations in non-small cell lung cancer patients from the Middle

Pierre Khoueiry1, Ghina Fakhri2, Reem Akel2

  • 1Department of Biochemistry and Molecular Genetics, American University of Beirut, Beirut, Lebanon.

Abstract

Insights

This study analyzed lung adenocarcinoma (LUAD) mutations in the Middle East using deep targeted sequencing. Most patients had at least one mutation, with FLT3, TP53, KRAS, and STK11 being frequently altered, providing crucial molecular insights.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Lung cancer survival rates remain low despite current treatments.
  • Targeted therapies necessitate routine driver mutation testing.
  • Next-generation sequencing (NGS) enables deep targeted sequencing for multi-genetic mutation detection.
  • The molecular landscape of non-small cell lung cancer (NSCLC) in the Middle East is understudied, with no prior deep targeted sequencing reports on lung adenocarcinoma (LUAD) tissues.

Purpose of the Study:

  • To perform deep targeted sequencing on LUAD tissues from the Middle East.
  • To identify common mutations in LUAD patients in this region.
  • To contribute to understanding the molecular pathology of LUAD.

Main Methods:

  • Deep targeted sequencing was conducted on 85 treatment-naive LUAD formalin-fixed paraffin-embedded tissues.
  • The TruSeq Amplicon Cancer panel, covering 48 genes, was utilized.
  • Variants with an allele frequency >10% were selected for analysis.

Main Results:

  • A total of 2,455 variants were identified, with missense mutations being the most common (75.6%).
  • All samples harbored at least one mutation in the top 10 most frequently mutated genes.
  • FLT3 showed the highest mutation rate (67%), followed by TP53, KRAS, and STK11. EGFR mutations were found in 22.4% of cases.

Conclusions:

  • This represents the first hotspot profiling study of LUAD patients from the Middle East.
  • Observed mutation frequencies align with previously reported outcomes.
  • The study confirmed the presence of at least one mutation in the investigated LUAD cohort.

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