Abstract 3179: ACB-PCR quantification of PIK3CA codon 1047 CAT to CGT mutant fraction in human tumor and non-tumor tissues
Authors: Yiying Wang, Meagan B. Myers, Fanxue Meng, Page B. McKinzie, Karen L. McKim, Barbara L. Parsons
Journal: Cancer Research (2011)

Abstract Phosphoinositide-3-kinase, catalytic, alpha polypeptide (PIK3CA) is a proto-oncogene encoding the p110 catalytic subunit of phosphoinositide 3-kinase (PI3K). A variety of tumors carry PIK3CA mutations. These mutations are thought to increase PI3K activity, increase cell proliferation, and may contribute to anti-cancer drug resistance. Three specific hotspot mutations within the PIK3CA gene are localized within the helical and kinase domains and account for &amp;gt;90% of all reported mutations in PIK3CA. One PIK3CA mutation in the kinase domain (codon 1047 CAT to CGT) accounts for more than 30% of all reported mutations. Because PIK3CA mutation may have clinical significance in terms of patient prognosis and treatment selection, we are using a sensitive allele-specific amplification approach called allele-specific competitive blocker-PCR (ACB-PCR) to analyze the PIK3CA codon 1047 CAT to CGT mutant fractions (MFs) in various human tissues. Specific goals of this study are to: 1) define normal and pathological levels of PIK3CA mutation in various human tissues, and 2) obtain data on the co-occurrence of PIK3CA mutation with other mutations (e.g., the KRAS codon 12 GAT and GTT mutations). To date, PIK3CA codon 1047 CAT to CGT MF has been measured in 50 human colon tissue samples, including 17 normal-appearing colonic mucosa samples, 13 normal tumor-adjacent samples, 10 adenomas, and 10 adenocarcinomas. The PIK3CA codon 1047 CAT to CGT mutation was present at measurable levels in all normal appearing colonic mucosa samples. The PIK3CA geometric mean MF in normal colonic mucosa ranged from 3.24 × 10-4 to 6.48 × 10-4, with an average (geometric mean) MF of 5.12 × 10-4. The PIK3CA geometric mean MFs measured in normal tumor-adjacent samples, adenomas, and adenocarcinomas were 6.45 × 10-4, 7.32 × 10-4, and 3.45 × 10-4, respectively. All colon tumors were found to carry PIK3CA codon 1047 CAT to CGT mutations as mutant subpopulations. The levels of PIK3CA mutation in normal-appearing colonic mucosa samples are similar to the levels of KRAS GAT mutation (∼10-4) measured previously in the same samples. Analyses of PIK3CA mutation in breast, pancreas, and thyroid are ongoing. In conjunction with analyses of other mutational targets, these types of data should aid in the identification of the best mutational biomarkers for particular tissues types (those mutations with consistently higher levels in tumors than in normal tissues). Also, by describing the prevalence of different molecular lesions within functional pathways related to carcinogenesis, the most promising molecular targets for therapeutic intervention will be identified. The contents of the abstract do not necessarily reflect the views or policies of the U.S. FDA. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3179. doi:10.1158/1538-7445.AM2011-3179