PIK3CA and breast cancer: Interestingly, the authors observed co-occurrence of gatekeeper and kinase domain variants (L512M, E513G, F517L, L547P) in cis. Although two variations affecting the same allele might be anticipated to be very rare, they are relatively common in breast cancer patients with alterations to the catalytic subunit of the phosphoinositide 3-kinase alpha (PI3Kα) complex, 95% carrying the double-variant E545K/E726K [57].