PIK3CA and cancer: Analysis of this gene in human tumor samples identified hotspot mutations in three sites, E542 and E545 in the helical domain (exon 9) and H1047 in the kinase domain (exon 20) (53), which induce activation of the alpha isoform of PI3K. Another gene contributing to increased cancer cell survival is BRAF, encoding a serine/threonine kinase protein and engaged MAPK pathway.