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. 2010 Apr 16;29(1):32.
doi: 10.1186/1756-9966-29-32.

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

Stefano Barbi  1 , Ivana Cataldo, Giovanni De Manzoni, Samantha Bersani, Simona Lamba, Silvia Mattuzzi, Alberto Bardelli, Aldo Scarpa
Affiliations

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

Stefano Barbi et al. J Exp Clin Cancer Res. .

Abstract

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.

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Figures

Figure 1
Figure 1
Point and 95% confidence interval estimates of prevalence of mutations affecting exon 9 and 20 of PI3KCA in 36 series. Mutations affecting exon 9 and 20 are shown as solid filled boxes and empty diamonds, respectively. The pooled estimates for each group are shown in grey.
See this image and copyright information in PMC

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