BIONADEGE: Genomic profiling of small bowel adenocarcinoma from the NADEGE prospective cohort.

Abstract

4140 Background: Small bowel adenocarcinoma (SBA) is a rare tumour. Large genomic analyses with prognostic assessments are lacking. Methods: BIONADEGE is an ancillary study of the NADEGE cohort that enrolled 347 patients (pts) with SBA from 2009 to 2012. Next generation sequencing investigates the presence of 740 hot spot somatic mutations in 46 genes involved in carcinogenesis. The MSI (MicroSatellite Instable) status was assessed using 5 microsatellites. The MMR (MisMatch Repair) status was assessed by immunochemistry (4 antibodies). Results: A total of 196 tumour samples were collected and 125 pts had conclusive results for mutation analysis. The clinical and tumours characteristics were comparable in the NADEGE and BIONADEGE cohort except for metastatic stage at diagnostic underrepresented in the BIONADEGE cohort (17.7%) due to missing tumour sample. A predisposing disease was reported in 25 (20.0%) cases (among them 14 Lynch syndromes and 7 Crohn diseases). The number of mutation observed was 0 in 9.6% pts, only 1 in 32.0%, 2 in 26.4% and ≥3 in 32.0%. The most frequent genomic alteration were KRAS (44.0%), TP53 (38.4%), PIK3CA (20.0%), APC (18.4%), SMAD4 (14.4%) and ERBB2 (7.2%). Altogether, a genomic alteration was observed in 90.3% of tumour. KRAS mutation were more frequent in synchronous metastatic tumour than in localized tumour (72.7% vs 38.2%, p = 0.003). There was no significant difference of mutation rate according to primary location for the most frequently altered gene. With caution to small sample, IDH1 mutation is more frequent and APC mutation never seen in Crohn disease. The rate of dMMR tumor was 38.6% in localized tumour and 0% in synchronous metastatic tumour. After a median follow-up of 55 months (95%CI [44-63]), M0 stage, pN0, pT1-2 were associate with better survival in univariate analysis. No significant prognostic value of genomic alteration was associated with OS. dMMR status was associate with a better prognosis for OS in pts with MMR status determined by immunohistochemistry (HR = 0.55 [0.29-1.01], p = 0.055). Conclusions: A high frequency of targetable alteration is observed in SBA. There is several specificities according to predisposing disease. No association between genomic alteration and prognostic was observed except a trend for a better prognosis associate with dMMR.