2023 World Conference on Lung Cancer (Posters)-P1.10. Enrichment of FA/HR Aberrations inATM/ATR-mutated NSCLC Was Accompanied by Distinct Molecular Features and Poor Prognosis

P1.10. Enrichment of FA/HR Aberrations inATM/ATR-mutated NSCLC Was Accompanied by Distinct Molecular Features and Poor Prognosis - PDF(Abstract)

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This presentation at the WCLC 2023 conference discusses the enrichment of FA/HR aberrations in NSCLC patients with ATM/ATR mutations. The authors conducted next-generation sequencing analyses on a cohort of 191 NSCLC patients with pathogenic ATM/ATR mutations and 308 NSCLC patients without these mutations. They found that patients with ATM/ATR mutations had higher mutational burdens and microsatellite instabilities, but not chromosomal instabilities. Additionally, KRAS mutations were enriched in ATM-mutated patients, while BRCA2 mutations, TP53 mutations, and ZNF703 amplification were enriched in ATR-mutated patients. Furthermore, patients with ATM/ATR mutations were more likely to acquire additional mutations in the Fanconi anemia and homologous recombination pathways. These additional mutations increased mutational loads and microsatellite instabilities, and patients with both ATM/ATR and FA/HR mutations had worse overall survival. The authors concluded that these findings help to better understand the molecular features and clinical implications of pathogenic ATM/ATR mutations in NSCLC. They also emphasize the importance of targeted therapies and/or immunotherapies for treating NSCLC patients with ATM/ATR mutations, particularly those with co-existing FA/HR aberrations.

Asset Subtitle

Yang Shao

Meta Tag

Speaker Yang Shao

Topic Tumor Biology: Translational Biology - Novel Targets

Keywords

WCLC 2023 conference

FA/HR aberrations

NSCLC patients

ATM/ATR mutations

next-generation sequencing

mutational burdens

microsatellite instabilities

KRAS mutations

BRCA2 mutations

overall survival