New Routes to Old Places: PIK3R1 and PIK3R2 Join PIK3CA and PTEN as Endometrial Cancer Genes

Summary: Cheung and colleagues identify PIK3R1 and PIK3R2, the genes encoding the α and β isoforms of the phosphatidylinositol 3-kinase (PI3K) p85 regulatory subunit, as additional mutation targets in endometrial cancer, and describe a novel mechanism leading to PTEN loss. Cancer Discovery; 1(2); 106–7. ©2011 AACR. IN THE SPOTLIGHT cancer model ( 9). This notion, supported by an initial analy-sis of the correlation between EC genetic alterations and cell line response to mTOR, PI3K, and mitogen-activated protein kinase inhibitors, will now open the way to a more rational combination of targeted therapies in advanced EC patients. Most importantly, this study also reveals a relatively high rate of mutations in the genes encoding the α and β isoforms of p85, PIK3R1 (20%) and PIK3R2 (5%). The mutation frequency of PIK3R1 in EC is much higher than previously found in other tumors, and confirms the results of a recent similar analysis performed on a smaller dataset ( 7). The rea