2024 World Conference on Lung Cancer (WCLC) - Posters-P1.06B.01 NSCLC in Patients with CTD-ILD: Apobec-Related Mutagenesis, Frequent TP53 Mutations and Paucity of Targetable Alterations

P1.06B.01 NSCLC in Patients with CTD-ILD: Apobec-Related Mutagenesis, Frequent TP53 Mutations and Paucity of Targetable Alterations

Back to course

Pdf Summary

The study explores the genomic characteristics of non-small cell lung cancer (NSCLC) in patients suffering from connective tissue disease-associated interstitial lung disease (CTD-ILD). This subgroup is noted for their heightened risk of developing lung cancer. The investigation leverages genomic data from 5,326 NSCLC patients to identify those with CTD or related interstitial pneumonia, culminating in a cohort of 56 pertinent cases. Among these, 15 patients exhibited CTD-ILD.<br /><br />Key findings underscore a distinct genomic landscape marked by frequent TP53 mutations—a common factor in many cancers—but a noticeable scarcity of targetable genetic alterations typically amenable to existing NSCLC therapies. Notably, targetable mutations in genes such as KRAS, BRAF, and EGFR, and those involving ALK, ROS1, RET, NTRK1/2/3, and MET, were infrequent in the studied CTD-ILD group.<br /><br />Additionally, there was a significant presence of APOBEC-related mutagenesis in this cohort. This mutational process, attributed to Apolipoprotein B mRNA Editing Catalytic Polypeptide-like (APOBEC) enzymes, points to a possible link between inflammation and cancer development in CTD-ILD patients. Such findings suggest that the inflammatory environment associated with CTD-ILD may provide a niche conducive to cancer pathogenesis.<br /><br />The study concludes that NSCLC in CTD-ILD patients, particularly those with minimal smoking history, exhibits unique mutational patterns, highlighting an urgent need for tailored therapeutic strategies that address the absence of common targetable alterations and the influence of inflammation-induced mutagenesis.

Asset Subtitle

Igor Odintsov

Meta Tag

Speaker Igor Odintsov

Topic Pathology & Biomarkers

Keywords

NSCLC

CTD-ILD

genomic characteristics

TP53 mutations

targetable genetic alterations

APOBEC mutagenesis

inflammation

cancer pathogenesis

therapeutic strategies

minimal smoking history