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Background   PIK3CA  is one of the genes most frequently mutated in human cancers and it is a potential target for personalized therapy. The aim of this study was to assess the frequency and type of  PIK3CA  mutations in gastric carcinoma and compare them with their clinical pathological correlates.    Methods  We analysed 264 gastric cancers, including 39 with microsatellite instability (MSI), for mutations in the two  PIK3CA  hotspots in exons 9 and 20 by direct sequencing of DNA obtained from microdissected cancer cells.    Results  The cases harbouring mutations were 42 (16%). All were heterozygous missense single base substitutions; the most common was H1047R (26/42; 62%) in exon 20 and the second was Q546K (4/42; 9.5%) in exon 9. All the mutated MSI cases (8/39) carried the H1047R mutation. No other association between  PI3KCA  mutations and their clinical pathological covariates was found. A metanalysis of the mutations occurring in the same regions presented in 27 publications showed that ratio between exon 20 and exon 9 prevalences was 0.6 (95% CI: 0.5 -0.8) for colon, 1.6 (95% CI: 1.1 -2.3) for breast, 2.7 (95% CI: 1.6 -4.9) for gastric and 4.1 (95% CI: 1.9 -10.3) for endometrial cancer.    Conclusions  The overall prevalence of  PIK3CA  mutations implies an important role for  PIK3CA  in gastric cancer. The lack of association with any clinical-pathological condition suggests that mutations in  PIK3CA  occur early in the development of cancer. The metanalysis showed that exon-selectivity is an important signature of cancer type reflecting different contexts in which tumours arise.

The analysis of PIK3CA mutations in gastric carcinoma and metanalysis of literature suggest that exon-selectivity is a signature of cancer type