WCLC 2025 - Posters & ePosters-EP.06.11 Comprehensive Genomic Profiling in Lung Cancer Management: Insights From North Sweden

Pdf Summary

This study by Karlowatz et al. from Umeå University, Sweden, presents a comprehensive genomic profiling of lung cancer patients in North Sweden, aiming to enhance clinical understanding and treatment decisions. Lung cancer remains the leading cause of cancer deaths in Sweden, with over 3,500 annual fatalities. Utilizing a 67-gene Archer VariantPlex panel for next-generation sequencing (NGS), the team analyzed 529 regional patients and compared data to a global cohort of 2,239.<br /><br />Key findings include comparable frequencies of TP53 and KRAS mutations between cohorts, but significantly lower EGFR and ERBB4 mutations in the Swedish group. Conversely, APC, ATM, and MET mutations were more frequent in Sweden. MET mutations were predominantly found in exon 14 with a unique variant (T992L) enriched locally. EGFR mutations clustered in known hotspots with differing subtype prevalence regionally. Subgroup analyses revealed that PTEN mutations in younger patients (<70) and RB1 mutations more common in males correlated with poorer survival, underscoring the importance of integrating patient age and gender in prognostic assessments.<br /><br />Importantly, single-gene survival impacts were influenced by co-mutations. For example, RB1 and TP53 combined with other mutations like TERT or MET worsened prognosis, while EGFR's favorable prognosis was negated when co-mutated with PTEN or MET. This suggests complex interplay through bypass signaling, loss of regulation, or apoptosis evasion mechanisms.<br /><br />The study also discovered 1,603 germline variants, with KIT M541L present in over 11% of patients. Notably, FOXL2 mutations in KIT M541L carriers were linked to significantly worse survival, highlighting germline-somatic mutation interactions.<br /><br />Conclusions emphasize the utility of broad NGS panels that include all genes of prognostic importance combined with demographic and clinical data to better capture lung cancer heterogeneity. The authors advocate for comprehensive mutation reporting to improve personalized clinical decision-making.

Asset Subtitle

Mikael Johansson

Meta Tag

Speaker Mikael Johansson

Topic Pathology and Biomarkers

Keywords

lung cancer

genomic profiling

Sweden

next-generation sequencing

TP53 mutations

KRAS mutations

EGFR mutations

MET mutations

prognostic biomarkers

germline variants