Frequent mutation of the PIK3CA gene in ovarian and breast cancers Journal Article
| Authors: | Levine, D. A.; Bogomolniy, F.; Yee, C. J.; Lash, A.; Barakat, R. R.; Borgen, P. I.; Boyd, J. |
| Article Title: | Frequent mutation of the PIK3CA gene in ovarian and breast cancers |
| Abstract: | Purpose: Activation of the phosphatidylinositol 3-kinase (PI3K)-AKT pathway, resulting in increased cell proliferation, survival, and motility, is believed to play an oncogenic role in many cancer types. The PIK3CA gene encodes the p110α catalytic subunit of PI3K, and is amplified in some ovarian cancers, whereas the AKT2 gene is amplified in some ovarian, breast, and pancreatic cancers. Recently, in a mutational screen of eight PI3K genes and eight PI3K-like genes, PIK3CA was found to be the only gene affected by somatic mutations, which were observed frequently in gastrointestinal and brain cancers. Here, we test whether PIK3CA is subject to mutation in ovarian and breast cancers. Experimental Design: Exons 9 and 20, encoding the highly conserved helical and kinase domains of PIK3CA, were subjected to sequence analysis in 198 advanced stage epithelial ovarian carcinomas and 72 invasive breast carcinomas (48 of ductal histology and 24 of lobular histology). Results: Somatic missense mutations were observed in 24 of 198 (12%) ovarian carcinomas, and in 13 of 72 (18%) breast carcinomas. Conclusions: These data indicate that mutations of PIK3CA play an oncogenic role in substantial fractions of ovarian and breast carcinomas, and in consideration of mutation of other components of the PI3K-AKT pathway in both tumor types, confirm the major oncogenic role of this pathway in ovarian and breast carcinomas. © 2005 American Association for Cancer Research. |
| Keywords: | controlled study; human tissue; gene mutation; gene sequence; human cell; sequence analysis; exon; missense mutation; mutation; exons; mutation, missense; ovarian neoplasms; gene; gene amplification; enzyme degradation; gene frequency; enzyme activation; breast neoplasms; breast carcinoma; 1-phosphatidylinositol 3-kinase; dna, neoplasm; ovary carcinoma; base sequence; models, molecular; protein structure, tertiary; binding sites; dna mutational analysis; catalytic domain; genetic code; pik3ca gene |
| Journal Title: | Clinical Cancer Research |
| Volume: | 11 |
| Issue: | 8 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2005-04-15 |
| Start Page: | 2875 |
| End Page: | 2878 |
| Language: | English |
| DOI: | 10.1158/1078-0432.ccr-04-2142 |
| PUBMED: | 15837735 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 176" - "Export Date: 24 October 2012" - "CODEN: CCREF" - "Source: Scopus" |
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