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(Slides)

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A study investigated the molecular features and prognosis of non-small cell lung cancer (NSCLC) patients with mutations in the ATM/ATR genes, which are involved in DNA damage response. The majority of ATM/ATR mutations are variants of uncertain significance, so their clinical and molecular characteristics in NSCLC have not been thoroughly studied. The research found that NSCLC patients with pathogenic mutations in ATM/ATR exhibited distinct clinical and molecular features. KRAS mutations were more common in ATM-mutated patients, while BRCA2 mutations, TP53 mutations, and ZNF703 amplification were enriched in ATR-mutated patients. Additionally, ATM/ATR-mutated NSCLC patients were more likely to have mutations in the FA/HR (Fanconi anemia/homologous recombination) pathways. These patients also had higher tumor mutation burden (TMB) and microsatellite instability (MSI), which are indicators of genetic instability. Furthermore, patients with both ATM/ATR and FA/HR mutations had even higher TMB and MSI and had a poorer prognosis. The study suggests that these findings can help in understanding the involvement of ATM and ATR in cancer and guide targeted therapies or immunotherapies for NSCLC patients with ATM/ATR mutations, particularly those with co-existing FA/HR aberrations. This research was supported by various funding sources, including the National Natural Science Foundation of China and the Natural Science Foundation of Jiangsu Province. The study highlights the importance of investigating the unique molecular patterns associated with specific gene mutations in NSCLC for better patient stratification and personalized treatment approaches.

Asset Subtitle

Yang Shao

Meta Tag

Speaker Yang Shao

Topic Tumor Biology: Translational Biology - Novel Targets

Keywords

non-small cell lung cancer

ATM/ATR genes

DNA damage response

KRAS mutations

BRCA2 mutations

TP53 mutations

ZNF703 amplification

tumor mutation burden

microsatellite instability

targeted therapies