Gene expression profiling of epidermal growth factor receptor/KRAS pathway activation in lung adenocarcinoma

摘要: We examined the genome-wide expression profiles of 86 primary lung adenocarcinomas and compared them with mutation status four key molecules (EGFR, ERBB2, KRAS BRAF) in EGFR/KRAS/BRAF pathway. Unsupervised classification revealed two subtypes (the bronchial type alveolar type) adenocarcinoma. Mutually exclusive somatic mutations epidermal growth factor receptor (EGFR) gene (36/86, 41.8%), K-ras (11/86, 12.8%) BRAF (1/86, 1.1%) were detected. observed significantly frequently bronchial-type tumors, whereas frequencies EGFR similar both types. Twenty-seven genes showed increased EGFR-mutated tumors these included that function pathway AKT1 BCR). In particular, BCR, which is required for protein degradation, was induced by EGF stimulation, suggesting a negative feedback loop cancer. A subgroup better prognosis than other tumors. Integrated analysis genetic profiling aimed to delineate inherent oncogenic pathways cancer will be valuable not only understanding molecular pathogenesis, but also discovering novel biomarkers predicting clinical outcome. (Cancer Sci 2007; 98: 985–991)