Gene Expression Changes in the Duodenal Adenoma-Carcinoma Sequence in Familial Adenomatous Polyposis (FAP)

Duodenal cancer is a leading cause of death in patients with FAP after colectomy. While cancer risk is up to 36% in Spigelman Stage IV patients, a significant proportion of cases occur in lower stage patients. Genome wide interrogation of APC-deficient mice revealed candidate biomarkers whose altered expression accompanied the evolution of small intestinal neoplasia. To date, no similar investigations have been pursued in FAP patients. In this study, a genome-wide transcriptional analysis of duodenal specimens from FAP patients was performed in order to describe changes occurring in the duodenal adenoma-carcinoma sequence in FAP Gene expression analysis was performed on duodenal samples of 12 FAP patients diagnosed with duodenal cancer (cases) between 1988-2014 and 12 FAP patients without duodenal cancer (controls). RNA was extracted from archived normal, adenoma and cancer tissue from cases and from archived adenoma tissue from controls. Gene expression profiling and analysis was performed using the Affymetrix Human Transcriptome Array 2.0. Three pairwise comparisons were conducted to describe the adenoma-carcinoma sequence: normal-adenoma (No-Ad), adenoma-cancer (Ad-Ca) and normal-cancer (No-Ca). To determine genes differentially expressed in FAP patients with duodenal cancer, adenoma from cases was compared with adenoma from controls (Ad-Ad). In total, 48 samples were analyzed, 36 from cases (normal, adenoma, cancer) and 12 from controls (adenoma).