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Detection of Targetable Alterations in Non-small Cell Lung Cancer using Next-generation Sequencing
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Detection of Targetable Alterations in Non-small Cell Lung Cancer using Next-generation Sequencing

Published on: October 10, 2025

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Mutational Profiling of Non-Small-Cell Lung Cancer Resistant to Osimertinib Using Next-Generation Sequencing in

Keke Nie1, Haiping Jiang2, Chunling Zhang3

  • 1Department of Radiotherapy, Qingdao Cancer Hospital, Qingdao 266042, China.

Biomed Research International
|May 2, 2018
PubMed
Abstract

Insights

EGFR C797S/G mutations, often on the same allele as T790M, are key to osimertinib resistance in non-small-cell lung cancer. Identifying these genetic changes guides future targeted therapies.

Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • Non-small-cell lung cancer (NSCLC) treatment often involves targeted therapies like osimertinib.
  • Acquired resistance to osimertinib is a significant clinical challenge, necessitating identification of underlying genetic mechanisms.
  • Understanding resistance mutations is crucial for developing effective subsequent treatment strategies.

Purpose of the Study:

  • To identify somatic mutations conferring resistance to osimertinib in advanced NSCLC.
  • To pinpoint optimal molecular targets for patients who develop resistance to osimertinib.
  • To analyze genetic alterations in Chinese NSCLC patients after osimertinib treatment failure.

Main Methods:

  • Study included advanced NSCLC patients with acquired resistance to osimertinib.
  • Tumor tissue was obtained via core needle biopsy after resistance developed.
  • Next-Generation Sequencing (NGS) was performed on DNA extracted from formalin-fixed paraffin-embedded (FFPE) samples to analyze genetic changes.

Main Results:

  • Among 9 Chinese NSCLC patients, NGS revealed various mutations including point mutations, altered gene copies, amplifications, and EML4-ALK fusion.
  • EGFR T790M mutations were maintained in 7 patients, with 5 developing secondary EGFR C797S and/or C797G mutations on the same allele.
  • No MET or HER2 amplification was detected. Treatment decisions were guided by NGS results, with 7 patients surviving at last follow-up.

Conclusions:

  • EGFR C797S/G mutations, co-occurring with EGFR T790M on the same allele, are a primary mechanism of osimertinib resistance in Chinese NSCLC patients.
  • Identifying these specific EGFR mutations is critical for understanding and overcoming osimertinib resistance.
  • Tumor cells that lose T790M but retain activating EGFR mutations may respond to first-generation EGFR-TKI therapy.

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