Molecular Profiling and Data Analysis of Lung Adenocarcinoma

Abstract

Abstract: Lung adenocarcinoma, a major cause of cancer-related deaths globally, was examined through a comprehensive analysis of 230 resected tumors. This study integrated various sequencing techniques to profile messenger RNA, microRNA, and DNA, along with evaluating copy number variations, methylation patterns, and proteomic data. The findings revealed a notable rate of somatic mutations (average of 8.9 mutations per megabase). Among the 18 significantly mutated genes were RIT1 activating mutations and newly identified MGA loss-of-function mutations, which were mutually exclusive with MYC amplification. Gender-based differences were observed, with EGFR mutations being more common in females and RBM10 mutations in males. Genetic abnormalities in NF1, MET, ERBB2, and RIT1 were detected in 13% of cases, often in tumors lacking other activated oncogenes, suggesting their potential driver roles. Splicing alterations were driven by somatic genomic changes, as evidenced by DNA and mRNA sequencing from the same tumor, including MET mRNA exon 14 skipping in 4% of cases. While MAPK and PI(3)K pathway activity was explained by known mutations in some cases, unexplained mechanisms appeared to activate the pathways in others. These findings lay the groundwork for understanding lung adenocarcinoma’s molecular basis and offer insights for classification and further investigations. Molecular profiling is crucial for identifying actionable mutations, guiding treatment choices in advanced adenocarcinoma and acquired resistance to tyrosine kinase inhibitors. Circulating tumor DNA sequencing gains importance in NSCLC diagnostics due to its accessibility, allowing longitudinal disease monitoring. Notably, the overall cancer death rate dropped by 27% between 1991 and 2016, resulting in around 2,629,200 fewer expected cancer deaths compared to peak death rates.