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Clinical Interest in Exome-Based Analysis of Somatic Mutational Signatures for Non-Small Cell Lung Cancer

Clinical Interest in Exome-Based Analysis of Somatic Mutational Signatures for Non-Small Cell Lung Cancer

Morgane Peroz ^1,2,3, Hugo Mananet ^1,2,3, Nicolas Roussot ⁴, Courèche Guillaume Kaderbhai ⁴, Valentin Derangère ^1,2,3, Caroline Truntzer ^1,2,3, François Ghiringhelli ^1,2,3,4

Morgane Peroz ^1,2,3, Hugo Mananet ^1,2,3, Nicolas Roussot ⁴

¹Platform of Transfer in Biological Oncology, Georges-Francois Leclerc Cancer Center-UNICANCER, 21000 Dijon, France.
²Unité de Formation et de Recherche des Sciences de Santé, University of Burgundy-Franche-Comté, 21000 Dijon, France.
³Unité Mixte de Recherche de l'Institut National de la Santé Et de la Recherche Médicale (INSERM) 1231, 21000 Dijon, France.
⁴Department of Medical Oncology, Georges François Leclerc Cancer Center-UNICANCER, 21000 Dijon, France.

⁰Platform of Transfer in Biological Oncology, Georges-Francois Leclerc Cancer Center-UNICANCER, 21000 Dijon, France.

Cancers +

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September 14, 2024

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View abstract on PubMed

Summary

This summary is machine-generated.

Whole exome sequencing (WES) reveals somatic mutational signatures in non-small cell lung cancer (NSCLC). Specific signatures predict poor response to standard therapies, guiding personalized treatment selection for advanced NSCLC patients.

Area Of Science

Oncology
Genomics
Cancer Research

Background

Non-small cell lung cancer (NSCLC) is a major cause of cancer mortality.
Understanding genomic alterations is crucial for improving NSCLC treatment outcomes.

Purpose Of The Study

To investigate the clinical utility of whole exome sequencing (WES) for analyzing somatic mutational signatures in advanced or metastatic NSCLC.
To correlate genomic features with patient response to standard of care treatments.

Main Methods

Analyzed exome sequencing data and clinical data from 132 advanced/metastatic NSCLC patients.
Evaluated single base substitutions (SBSs), double base substitutions (DBSs), and copy number signatures.
Assessed tumor mutational burden (TMB), neoantigens, TCR clonality, homologous recombination deficiency (HRD), copy number alterations (CNAs), and microsatellite instability (MSI).

Main Results

Identified specific somatic mutational signatures in NSCLC.
Found associations between genomic features, NSCLC subtypes, and patient survival (progression-free and overall survival).

Conclusions

Whole exome sequencing provides valuable insights into NSCLC mutational landscape.
Specific signatures correlate with poor response to immune checkpoint inhibitors (ICIs) and chemotherapy.
Genomic profiling can aid in selecting appropriate therapies and identifying non-responders.

Keywords:

immune checkpoint inhibitors non-small cell lung cancer prognostic biomarkers somatic mutational signatures whole exome sequencing

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