| Summary: | <p>Abstract</p> <p>Background</p> <p>Activation of the phosphatidylinositol 3-kinase (PI3K) through mutational inactivation of <it>PTEN </it>tumour suppressor gene is common in diverse cancer types, but rarely reported in gastric cancer. Recently, mutations in <it>PIK3CA</it>, which encodes the p110α catalytic subunit of PI3K, have been identified in various human cancers, including 3 of 12 gastric cancers. Eighty percent of these reported mutations clustered within 2 regions involving the helical and kinase domains. <it>In vitro </it>study on one of the "hot-spot" mutants has demonstrated it as an activating mutation.</p> <p>Methods</p> <p>Based on these data, we initiated <it>PIK3CA </it>mutation screening in 94 human gastric cancers by direct sequencing of the gene regions in which 80% of all the known <it>PIK3CA </it>mutations were found. We also examined <it>PIK3CA </it>expression level by extracting data from the previous large-scale gene expression profiling study. Using Significance Analysis of Microarrays (SAM), we further searched for genes that show correlating expression with <it>PIK3CA</it>.</p> <p>Results</p> <p>We have identified <it>PIK3CA </it>mutations in 4 cases (4.3%), all involving the previously reported hotspots. Among these 4 cases, 3 tumours demonstrated microsatellite instability and 2 tumours harboured concurrent <it>KRAS </it>mutation. Data extracted from microarray studies showed an increased expression of <it>PIK3CA </it>in gastric cancers when compared with the non-neoplastic gastric mucosae (<it>p </it>< 0.001). SAM further identified 2910 genes whose expression levels were positively associated with that of <it>PIK3CA</it>.</p> <p>Conclusion</p> <p>Our data suggested that activation of the PI3K signalling pathway in gastric cancer may be achieved through up-regulation or mutation of <it>PIK3CA</it>, in which the latter may be a consequence of mismatch repair deficiency.</p>
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