| Summary: | <p>Abstract</p> <p>Background</p> <p><it>PIK3CA </it>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 <it>PIK3CA </it>mutations in gastric carcinoma and compare them with their clinical pathological correlates.</p> <p>Methods</p> <p>We analysed 264 gastric cancers, including 39 with microsatellite instability (MSI), for mutations in the two <it>PIK3CA </it>hotspots in exons 9 and 20 by direct sequencing of DNA obtained from microdissected cancer cells.</p> <p>Results</p> <p>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 <it>PI3KCA </it>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.</p> <p>Conclusions</p> <p>The overall prevalence of <it>PIK3CA </it>mutations implies an important role for <it>PIK3CA </it>in gastric cancer. The lack of association with any clinical-pathological condition suggests that mutations in <it>PIK3CA </it>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.</p>
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