Molecular Context of the EGFR Mutations: Evidence for the Activation of mTOR/S6K Signaling

摘要: Purpose: Activating somatic mutations in the epidermal growth factor receptor ( EGFR ) gene are present a small subset of lung adenocarcinomas. These cluster specific regions and confer sensitivity to inhibitors tyrosine kinase activity EGFR. To further determine genetic molecular characteristics tumors carrying mutations, we investigated status adenocarcinomas evaluated its association with patients tumors, such as at KRAS p53, ErbB2 amplification, levels HER2 proteins, downstream effectors EGFR, phospho–extracellular signal-regulated phospho-S6 proteins. Experimental Design: The mutational was determined by direct sequencing 86 primary 12 cancer cell lines, correlated number variables relating tumor patient. A tissue microarray containing 37 constructed determine, fluorescence situ hybridization analysis, copies genes and, immunohistochemistry, HER2, phospho-ERK, Results: were identified 13% tumors. type clustering identical those previously reported. Amplification occurred 14% could arise mutations. Interestingly, mTOR activation, measured indirectly augmented protein, more frequent alterations either or P = 0.00005; Fisher9s exact test) than their wild-type counterparts. Conclusions: Our data agree accumulation cancer. Moreover, report amplification -mutant positive correlation between activation signaling.