Abstract 4379: Somatic exomic landscape of small intestinal adenocarcinomas
Authors: Hänninen Ulrika A. , Katainen Riku , Hamberg Jiri , Mecklin Jukka-Pekka , Forsström Linda , Pitkänen Esa , Mäkinen Netta , Aaltonen Lauri A. 
Published: July 2017

Abstract
The small intestine makes up 75% of the length of the alimentary tract, however, small intestinal tumors constitute less than 5% of gastrointestinal tumors. Of small intestinal tumors, around one third are aggressive adenocarcinomas with poor outcome (5-year survival rate is approximately 30%). Reasons for their rarity are still unclear. Predisposing factors include Crohn´s disease, celiac disease, hereditary genetic syndromes such as familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC), and dietary factors. Due to the low incidence of small intestinal adenocarcinomas (SIAs), the number of genetic studies remains insufficient. Since there are limited data available to guide the therapeutic decisions, our aim is to characterize the somatic mutational landscape of SIAs in a population-based material using exome sequencing.
We collected information on all patients diagnosed with SIA in Finland between the years 2004-2011 utilizing the Finnish Cancer Registry. This registry maintains a nation-wide database on all cancer cases diagnosed in Finland since 1953. From these we selected all cases with 1) confirmed small intestinal primary tumor, 2) available tumor material, and 3) the tumor content of at least 50%. In order to focus solely on small intestinal tumors, we excluded tumors of the papillary region since they might also have arisen from the pancreas or the biliary tract. Altogether 107 tumors representing all three parts of the small intestine were selected for exome sequencing. The tumor data was filtered against the ExAC and SISU databases to remove germline variations. In addition, Sanger sequencing of the corresponding normal tissue will be used to verify the somatic origin of the most interesting observed mutations. The data analysis is ongoing. The average number of mutations in a tumor was 358 (range 40 - 4,166). Preliminary results show that the most frequently mutated known cancer genes were TP53 (42%) and KRAS (31%). We will identify all the most frequently mutated genes, compare the mutational patterns between the three different sections of the small intestine, and further characterize their similarities to gastric and colorectal adenocarcinomas. We will also analyze the association between the discovered mutations and patients’ survival time. This comprehensive characterization of the molecular basis of SIAs will provide better insight on how these tumors arise and possibly how they should be treated.
Citation Format: Ulrika A. Hänninen, Riku Katainen, Jiri Hamberg, Jukka-Pekka Mecklin, Linda Forsström, Esa Pitkänen, Netta Mäkinen, Lauri A. Aaltonen. Somatic exomic landscape of small intestinal adenocarcinomas [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 nr 4379. doi:10.1158/1538-7445.AM2017-4379