Comprehensive genomic profiling of synchronous invasive adenocarcinoma and squamous cell carcinoma within the same lobe: a case report

Background: Synchronous multiple primary lung cancers are rare. The field cancerization model posits that carcinogen exposure leads to molecular damage and epigenetic reprogramming in the bronchial epithelium, predisposing individuals to multiple tumors. However, genetic factors may explain why only some individuals develop synchronous primaries. Whole genome sequencing (WGS) offers comprehensive insights into somatic mutations, structural variants, and DNA repair defects, surpassing the limitations of histology or exome sequencing. Case Description: ) pathways, both pivotal in tobacco-related mutagenic resistance. Oncogenic pathway analysis showed distinct alterations: adenocarcinoma was enriched in MET pathway alterations, while the squamous carcinoma exhibited alterations in alternative pathways. Conclusions: alterations provides mechanistic evidence of genetic vulnerability, highlighting the importance of counseling, surveillance, and potential DNA repair-targeted strategies.