PIK3CA Gene Mutations And Amplifications In Chinese Patients With Ovarian Clear Cell Carcinoma

Background Genetic alterations in PIK3CA gene have been found in many humantumors, but their roles have not been fully explored in ovarian clear cell carcinoma. Thepresent study was undertaken to assess mutations and amplifications of PIK3CA inChinese patients with ovarian clear cell carcinoma.Methods DNA sequencing and real-time quantitative PCR of the most commonlymutated exons9and20of PIK3CA in human cancer were used to examine mutationsand amplifications, respectively, on genomic DNA samples isolated from51cases. Thebiological significance of novel PIK3CA mutation was examined by exogenouslyexpressing mutant construct in cells and analyzing the level of AKT phosphorylation.Results Activating missense mutations of PIK3CA were found in9(17.6%) cases.Six cases have mutation E545A in exon9and2cases have mutation H1047R in exon20. Another novel mutation was identified at Thr544in exon9which results in asubstitution of threonine for proline (T544P). We analyzed the biological effect ofmutant T544P and found that T544P can increase AKT phosphorylation in cell culture.In addition, amplifications of PIK3CA were observed in6cases of ovarian clear cellcarcinoma (11.8%). PIK3CA mutations and amplifications are mutually exclusive.Conclusion Our study demonstrates relatively low frequency of PIK3CA mutationsand amplifications in ovarian clear cell carcinoma. However, PIK3CA alteration maystill play a role in some subset of ovarian clear cell carcinoma.