2024 World Conference on Lung Cancer (WCLC) - Posters-P1.01B.02 The Genomic Landscape of Lung Cancer in Never-Smokers from the Women's Health Initiative

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This study, conducted by researchers from Fred Hutchinson Cancer Center and Dana-Farber Cancer Institute, focuses on the genomic characterization of lung adenocarcinoma in older female never-smokers compared to heavy-smokers. Utilizing samples from the Women’s Health Initiative, the study analyzes genetic mutations in lung tumor and normal tissue pairs through whole-exome sequencing, whole genome sequencing, and targeted sequencing. <br /><br />The research highlights that both never- and heavy-smokers share common features of lung adenocarcinoma, such as aneuploidy, while distinct genetic differences exist between the groups. Somatic copy number alterations did not significantly vary with smoking status, suggesting a shared chromosome-level instability.<br /><br />Mutational signatures indicate clock-like and APOBEC signatures are common across never-smokers, with no significant difference in quantity when juxtaposed with heavy-smokers. Notably, there are differences in oncogenic mutations: EGFR mutations were more frequent in never-smokers, whereas KRAS mutations were common in heavy-smokers. MGA mutations were exclusive to smokers, while MET mutations appeared only in non-smokers.<br /><br />The study finds that ALK, RET, and ROS1 fusions, prevalent in younger never-smokers, were absent in this cohort of older women. This suggests a variation in genomic landscape influenced by age. Moreover, distinct mutational patterns align with differing kinase mutation targets such as EGFR and KRAS, impacting targeted therapy strategies.<br /><br />In conclusion, the research underscores the necessity for personalized treatment approaches in lung adenocarcinoma based on specific mutational profiles influenced by smoking status, emphasizing focused therapeutic strategies for targeted mutations like EGFR and KRAS. While significant associations with mutagenesis signatures were identified, broader patterns of genome alteration, such as aneuploidy, appeared unaffected by smoking history. This study adds to understanding the complex genomic landscape of lung adenocarcinoma, particularly among never-smoking, post-menopausal women.

Asset Subtitle

Sitapriya Moorthi

Meta Tag

Speaker Sitapriya Moorthi

Topic Risk Factors, Risk Reduction & Tobacco Control

Keywords

lung adenocarcinoma

genomic characterization

never-smokers

heavy-smokers

EGFR mutations

KRAS mutations

aneuploidy

mutational signatures

targeted therapy

personalized treatment