Frequent mutations and amplifications of the PIK3CA gene in pituitary tumors

<jats:p>Genetic alterations in the <jats:italic>PIK3CA</jats:italic> gene of the phosphoinositide 3-kinase (PI3K)/AKT pathway have been found in many human tumors, but they have not been explored in pituitary tumors. We undertook the present study to explore mutations and amplifications of the <jats:italic>PIK3CA</jats:italic> gene in pituitary tumors. DNA sequencing and real-time quantitative PCR were used to examine mutations and amplifications respectively, on genomic DNA samples isolated from 353 cases of pituitary tumors, and immunohistostaining was used to assess PIK3CA expression. About 8 out of 91 (9%) invasive pituitary tumors versus 0 out of 262 (0%) noninvasive tumors were found to harbor somatic mutations in exons 9 and 20 of the <jats:italic>PIK3CA</jats:italic> gene (<jats:italic>P</jats:italic><0.001), and the mutation was associated with increased disease recurrence. Genomic <jats:italic>PIK3CA</jats:italic> amplifications (defined as ≥4 copies) were observed in both invasive and noninvasive tumors, with a prevalence of around 20–40% in various types of pituitary tumors. PIK3CA protein overexpression was observed in cases with high <jats:italic>PIK3CA</jats:italic> copy number. <jats:italic>RAS</jats:italic> mutations were also examined and found in 6 out of the 91 (7%) invasive tumors. <jats:italic>PIK3CA</jats:italic> amplifications were mutually exclusive with <jats:italic>PIK3CA</jats:italic> or <jats:italic>RAS</jats:italic> mutations (<jats:italic>P</jats:italic><0.001). This study demonstrated for the first time relatively common <jats:italic>PIK3CA</jats:italic> mutations and amplifications as well as <jats:italic>RAS</jats:italic> mutations and their tendency of mutual exclusivity in pituitary tumors. The data provide strong genetic evidence supporting a role of the PI3K/AKT signaling pathway in the tumorigenesis of pituitary tumors, particularly the invasive types.</jats:p>