89PDistribution of somatic mutations in PIK3CA gene in breast colorectal and colorectal Czech cancer patients - selected colorectal cancer patients with angiogenesis inhibitors treatment

Abstract Background Mutation profiling of tumours for treatment options is reality in many types of cancer and biomarkers eg. KRAS, EGFR are well established in personalised medicine. Phosphatidyl 3-kinases (PI3K) are a family of lipid kinases involved in many cellular processes, including cell growth, proliferation, differentiation, motility, and survival. Mutation of PIK3CA gene has been implicated in the pathogenesis of several cancers, but their prognostic/predictive/therapeutic implications are still controversial. Methods From 2008-2019, 2158 colorectal (involving subgroup of 118 patients treated with antiVEGF) and 332 breast cancer samples were enrolled. Analysis of selected somatic mutations of PIK3CA gene in exon 9 (codons 542, 545) and exon 20 (codon 1047) were determined by primer extension method. Results Mutations in PIK3CA gene were detected in 11,7% (252/2054) of the colorectal cancer (14,4% in antiVEGF subgroup). There was unequal distribution of mutations between the exon 9 (73,6%) and exon 20 (26,4%), in antiVEGF subgroup - exon 9 (64,7%), exon 20 (35,3%). Coexistence with mutations in other predictive markers like KRAS and BRAF gene was also detected (6,8% KRAS and PIK3CA, 1,1% BRAF and PIK3CA). In breast cancer samples frequency of PIK3CA mutations was detected in 27,7% (92/332). Mutations in the exons 9 and 20 of PIK3CA gene were detected in 42,4% and 57,6%, respectively. Conclusions In our cohorts of colorectal (subgroup patients with antiangiogenesis inhibitors treatment included) and breast cancer patients, frequency of PIK3CA mutations are in range and correlates with published data. There is unequal distribution of PIK3CA mutations between these two types of cancer and also between localisation (exons) of mutations. Currently no sufficient evidence to recommend routine genotyping of PIK3CA in clinical practice. So still further studies are warranted to evaluate their real prognostic/predictive role and potential benefit in clinical practice. Supported by: AZV CR, No.16-32198A: Genetic and epigenetic predictive biomarkers of treatment success for angiogenesis inhibitors in colorectal carcinoma. Legal entity responsible for the study The authors. Funding AZV CR, No.16-32198A. Disclosure All authors have declared no conflicts of interest.