P-175 Next-generation sequencing in colorectal cancer patients: Characterization and prognostic implications

The recently published ESMO guideline for metastatic colorectal cancer (CRC) recommends testing the current validated biomarkers (MMR, KRAS, NRAS and BRAF) to guide precision medicine in CRC. Next-generation sequencing (NGS) is a useful tool identify new predictive prognostic biomarkers. We conducted retrospective observational study 250 patients treated at Gastrointestinal Tumours Unit Ramon y Cajal University Hospital, which tissue NGS was performed (Foundation Medicine Oncomine tests). Cox regression analysis used prognosis of molecular with STATA-15 software. Characteristics tumours included: 166 CRC, 49 gastroesophageal (GEC), 20 unknown origin (CUP) 15 other gastrointestinal (GIC). number genes pathogenic genomic alterations 291 195 GEC, 114 CUP 101 GIC. distribution altered frequency over 15% was: TP53 77%, APC 71%, GNAS 21%, ASXL1 19%, KRAS 18%, FLT1 17%, ZNF217 BRCA2 16% AURKA 15%. clinical characteristics CRC were as follows: median age 61.8 years; 61.4% female; OS 41.9 months 69.7% dead time this analysis. baseline pattern before 13.3% mutated; 1.2% 1.2 BRAF 21.1% HER2 positive; 0.7% dMMR. Female gender (HR 1.5; p=0.044), basal mutation 2.5; p < 0.001) 7.1; p=0.008) indicators significant poor prognosis. In 38 (22.8%), potentially targetable gene identified, guided therapy administered 39.5% them. found non-statistically trend towards better 0.63; 95%CI 0.28-1.45). univariate identified 36 (p 0.05): BCL6, BRAF, CCND2, CIC, CTNNA1, DOT1L, ERCC4, ERG, EZH2, FANCL, FBXW7, GNA13, GSK3B, HNF1A, JAK2, KEL, MAPK1, MEN1, MERTK, MET, MLH1, MTOR, NOTCH3, P2RY8, PTCH1, PTPN11, RAD54L, RICTOR, SMAD4, SRC, STAG2, TNFAIP3, TSC1, TSC2 WHSC1. signature combining three independent factors (ERCC4, RAD54L SMAD4), able predict survival outcomes our cohort multivariate higher than tumours. Although without available targeted therapy, occur more 70% patients. study, including SMAD4; provided information.