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Abstract 2728: Frequency and prognostic value of PI3KCA mutations in early stage of colorectal cancer in Mexican patients

Background: There are molecular associations between mutated profiles and microsatelital instability, both related with tumor growth and oncogenic development by activating tyrosine receptors families in colorectal cancer (CRC). It is known that exon 9 and exon 20 (H1047R) mutations in PIK3CA increa...

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Published in:Cancer research (Chicago, Ill.) Ill.), 2017-07, Vol.77 (13_Supplement), p.2728-2728
Main Authors: Ruiz-Garcia, Erika, Ortega, Alette, Bahena, Antonio, Fernandez, Edith, Calderillo, German, Camarillo, Cesar Lopez, Marchat, Laurence, Guadarrama, Jorge, Meneses-Garcia, Abelardo, Vega, Horacio Astudillo-de la
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Summary:Background: There are molecular associations between mutated profiles and microsatelital instability, both related with tumor growth and oncogenic development by activating tyrosine receptors families in colorectal cancer (CRC). It is known that exon 9 and exon 20 (H1047R) mutations in PIK3CA increased PI3K activity. Moreover, PIK3CA mutations are significantly associated with tumor recurrence and poor overall survival. The frequency of PIK3CA mutations in CCR occurs in 15-20%, being the catalytic subunit more frequently affected. The aim of our study was to investigate the frequencies and clinical implications of these genetic alterations in advanced CRC. Methods: Retrospectively, we analyzed the initial paraffin embedded tissue block of 71 Mexican patients with CCR stage II. We evaluated mutations frequency of PIK3CA exon 9 (E542K, E545K) and exon 20 (H1047R) using qBiomarker Somatic Mutation PCR for real-time PCR-based. These methodology increases specificity, multiplex PCR and allelic discrimination. The data analysis was done using Ct values and Analysis Webportal. Results: We found in our population a frequency of PIK3CA mutations of 26%. Of those, double mutants were present in 7% with a higher frequency for E545K/H1047R. Clinical implication that we found is that any active mutation of PIK3CA is associated to an increase of recurrence risk (HR 1.86;CI 95% =0.46-7.5), but most important is for E545K mutation (HR 4.17; CI 95% 0.85-20.39), meanwhile comparing no mutated with H1074R mutated samples there were no differences in HR (0.53 vs. 0.60, respectively). Conclusions: We found a higher number of PI3KCA mutations that literature reports and that E545K mutation have a worst prognostic implication but we need to increase our sample looking for statistical significance results. Data from H1047R mutation raise de hypothesis that it could exist a compensatory mechanism related to structural interactions between both helicoidal and catalitic domains. Citation Format: Erika Ruiz-Garcia, Alette Ortega, Antonio Bahena, Edith Fernandez, German Calderillo, Cesar Lopez Camarillo, Laurence Marchat, Jorge Guadarrama, Abelardo Meneses-Garcia, Horacio Astudillo-de la Vega. Frequency and prognostic value of PI3KCA mutations in early stage of colorectal cancer in Mexican patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract
ISSN:0008-5472
1538-7445
DOI:10.1158/1538-7445.AM2017-2728