Importantly, we have the first time revealed significant associations of gene methylation with PIK3CA amplification in NSCLC, which is consistent with a model which aberrant methylation and hence silencing of a number of tumor-related genes, which coexisted with activating genetic alterations of PI3K/Akt pathway, may be a consequence of overactivation of this pathway. Here, PIK3CA is linked to non-small cell lung carcinoma.