Mutations of <it>PIK3CA </it>in gastric adenocarcinoma
<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...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2005-03-01
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| Series: | BMC Cancer |
| Online Access: | http://www.biomedcentral.com/1471-2407/5/29 |
| _version_ | 1818386633747070976 |
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| author | So Samuel Chu Kent-Man Zhao Wei Chan Agnes Chan Tsun Wong Chi Li Vivian Chen Xin Yuen Siu Leung Suet |
| author_facet | So Samuel Chu Kent-Man Zhao Wei Chan Agnes Chan Tsun Wong Chi Li Vivian Chen Xin Yuen Siu Leung Suet |
| author_sort | So Samuel |
| collection | DOAJ |
| description | <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> |
| first_indexed | 2024-12-14T03:57:09Z |
| format | Article |
| id | doaj.art-6bd04d57b9f142d7b6cd977556bb3c4b |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-14T03:57:09Z |
| publishDate | 2005-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-6bd04d57b9f142d7b6cd977556bb3c4b2022-12-21T23:18:04ZengBMCBMC Cancer1471-24072005-03-01512910.1186/1471-2407-5-29Mutations of <it>PIK3CA </it>in gastric adenocarcinomaSo SamuelChu Kent-ManZhao WeiChan AgnesChan TsunWong ChiLi VivianChen XinYuen SiuLeung Suet<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>http://www.biomedcentral.com/1471-2407/5/29 |
| spellingShingle | So Samuel Chu Kent-Man Zhao Wei Chan Agnes Chan Tsun Wong Chi Li Vivian Chen Xin Yuen Siu Leung Suet Mutations of <it>PIK3CA </it>in gastric adenocarcinoma BMC Cancer |
| title | Mutations of <it>PIK3CA </it>in gastric adenocarcinoma |
| title_full | Mutations of <it>PIK3CA </it>in gastric adenocarcinoma |
| title_fullStr | Mutations of <it>PIK3CA </it>in gastric adenocarcinoma |
| title_full_unstemmed | Mutations of <it>PIK3CA </it>in gastric adenocarcinoma |
| title_short | Mutations of <it>PIK3CA </it>in gastric adenocarcinoma |
| title_sort | mutations of it pik3ca it in gastric adenocarcinoma |
| url | http://www.biomedcentral.com/1471-2407/5/29 |
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