This study provides a comprehensive molecular profiling of 230 lung adenocarcinomas using messenger RNA, microRNA, and DNA sequencing, integrated with copy number, methylation, and proteomic analyses. High rates of somatic mutations were observed (mean 8.9 mutations per megabase), with 18 genes significantly mutated, including *RIT1* activating mutations and newly described *MGA* loss-of-function mutations, which are mutually exclusive with focal MYC amplification. *EGFR* mutations were more frequent in female patients, while *RBMI0* mutations were more common in males. Aberrations in *NF1*, *MET*, *ERBB2*, and *RIT1* occurred in 13% of cases and were enriched in samples lacking an activated oncogene, suggesting a driver role in certain tumors. DNA and mRNA sequence analysis highlighted splicing alterations driven by somatic genomic changes, including exon 14 skipping in *MET* mRNA in 4% of cases. MAPK and PI(3)K pathway activity, measured at the protein level, was explained by known mutations in only a fraction of cases, indicating additional, unexplained mechanisms of pathway activation. These findings establish a foundation for classification and further investigations into the molecular pathogenesis of lung adenocarcinoma.This study provides a comprehensive molecular profiling of 230 lung adenocarcinomas using messenger RNA, microRNA, and DNA sequencing, integrated with copy number, methylation, and proteomic analyses. High rates of somatic mutations were observed (mean 8.9 mutations per megabase), with 18 genes significantly mutated, including *RIT1* activating mutations and newly described *MGA* loss-of-function mutations, which are mutually exclusive with focal MYC amplification. *EGFR* mutations were more frequent in female patients, while *RBMI0* mutations were more common in males. Aberrations in *NF1*, *MET*, *ERBB2*, and *RIT1* occurred in 13% of cases and were enriched in samples lacking an activated oncogene, suggesting a driver role in certain tumors. DNA and mRNA sequence analysis highlighted splicing alterations driven by somatic genomic changes, including exon 14 skipping in *MET* mRNA in 4% of cases. MAPK and PI(3)K pathway activity, measured at the protein level, was explained by known mutations in only a fraction of cases, indicating additional, unexplained mechanisms of pathway activation. These findings establish a foundation for classification and further investigations into the molecular pathogenesis of lung adenocarcinoma.