PTEN and cancer: This lead us to suspect that PIK3CA mutations are intertwined with PTEN transcriptional activity, which may indicate that 1) upregulation of PTEN expression was a cellular response to earlier cancer-driving events prior to PIK3CA mutation, and positive selection for PIK3CA mutations enabled tumors to ameliorate the suppressive effects of PTEN upregulation, or 2) PIK3CA mutations initially resulted in an early survival advantage but was eventually suppressed by upregulated PTEN expression as part of a protective cellular response.