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Updated: Mar 22, 2026
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Genetic changes of non-small cell lung cancer under neoadjuvant therapy
Arne Warth1, Volker Endris1, Albrecht Stenzinger1
1Institute of Pathology, Heidelberg University, Heidelberg, Germany.
Background:
Large scale sequencing efforts defined common molecular alterations in non-small cell lung cancer (NSCLC) and revealed potentially druggable mutations. Yet, systematic data on the changes of the respective molecular profiles under standard therapy in NSCLC are limited.
Results:
14 out of 68 observed coding mutations (21%) and 6 out of 33 (18%) copy number variations (CNV) were lost or gained during therapy. Mutational and CNV changes clustered in 6/37 (16%) and 3/37 (8%) patients. Changes in clinically relevant mutations were rare but present in single cases for genes such as BRAF and PIK3CA. The type of radiochemotherapy but not the duration of therapy impacted on the frequency of mutational changes.
Methods:
We established a lung cancer specific next-generation sequencing panel covering ~7500 hotspots of 41 genes frequently mutated in NSCLC and performed ultradeep multigene sequencing of 37 corresponding pre- and post-therapeutic formalin fixed paraffin-embedded specimens to discover mutational changes and copy number variations under neo-adjuvant radio- (RTX) and/or chemotherapy (CTX).
Conclusion:
We unraveled changes in common driver gene candidates in NSCLC under neo-adjuvant therapy. Our data shed first light on the genetic changes of NSCLC under conventional therapy and might be taken into account when the relevance of sequential biopsy approaches is discussed.
Insights
Molecular profiles of non-small cell lung cancer (NSCLC) can change during therapy. This study identified specific mutations and copy number variations that were altered following neoadjuvant radiochemotherapy in NSCLC patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Large-scale sequencing has identified common molecular alterations in non-small cell lung cancer (NSCLC), including druggable mutations.
- However, data on how these molecular profiles change during standard NSCLC therapy are limited.
Purpose of the Study:
- To investigate molecular profile changes in NSCLC patients undergoing neoadjuvant radiochemotherapy.
- To identify alterations in mutations and copy number variations (CNVs) before and after treatment.
Main Methods:
- Developed a lung cancer-specific next-generation sequencing panel targeting ~7500 hotspots in 41 NSCLC genes.
- Performed ultradeep sequencing on 37 pre- and post-therapy NSCLC tumor specimens.
Main Results:
- Approximately 21% of coding mutations and 18% of copy number variations (CNVs) were altered during therapy.
- Mutational and CNV changes were observed in 16% and 8% of patients, respectively.
- Changes in clinically relevant mutations (e.g., BRAF, PIK3CA) were rare but occurred; radiochemotherapy type, not duration, influenced mutation frequency.
Conclusions:
- Neoadjuvant therapy can induce changes in common driver gene candidates in NSCLC.
- These findings provide initial insights into NSCLC genetic alterations under conventional therapy.
- The results may inform discussions regarding the utility of sequential biopsy approaches in NSCLC management.
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