P-241 Feasibility and results of expanded RAS genotyping in an Argentiean public hospital

Introduction: The clinical significance of KRAS gene for colorectal cancer patients has been established in randomized clinical trials. Thus, testing for KRAS codons 12 and 13 were recommended. The mutations in these codons predict lack of response to anti-EGFR therapies. However, even among patients whose tumors are wild type for KRAS codons 12 and 13, only a subset respond to therapy. Since additional activating mutations downstream of EGFR may also play a role in treatment strategies, we launched a multidisciplinary team to improve the genomic characterization of tumors. We evaluate the feasibility and results for extended RAS analysis in colorectal tumors from public hospitaĺs patients Methods: Prospective analysis of 80 formalin fixed paraffin embedded (FFPE) samples of colorectal adenocarcinoma, of patients admitted between January and December of 2014. We used Sanger direct sequencing by capillary electrophoresis (ABI ®) to analyzed the mutational status of KRAS and NRAS genes Results: We detected 41 (51%) samples KRAS WT/NRAS WT; 34 (43%) KRAS MUTATED/NRAS WT and 5 (6%) KRAS WT/ NRAS MUT. In KRAS gene, we found mutations in: 59% codon 12; 14% codon 13; 15% codon 61; 3% codon 117 and 9% codon 146. In NRAS gene, we found codons 12, 13 and 61 mutations. In total, 14/80 (17,5%) tumors wild type for KRAS codons 12 and 13 harbored a mutation in another of the RAS pathway genes. The mutations in both genes were mutually exclusive. The mutations frequencies detected in both genes are similar with those reported in the international literature Conclusion: RAS genotyping was feasible as quality measure from a multidisciplinary team. In our series NRAS genotype criteria should be used together with KRAS genotype to select patients who will likely benefit from targeted therapy. These data confirm the good practice of achieving genotyping the complete RAS for more complete prognostic and predictive molecular characterization of the tumor, with implications for strategy approach to patients. This should be a standard of care.