Identification of candidate genes in ulcerative colitis and Crohn's disease using cDNA array technology

Inflammatory bowel disease (IBD) follows a multigenic mode of inheritance, encompassing the clinically discrete phenotypes of ulcerative colitis (UC) and Crohn's disease (CD). The risk of malignant transformation of the colon increases with the duration and extent of IBD and is particularly high for patients with a longstanding history of UC. We wished to identify candidat e genes that might be involved in disease pathogenesis based on functional plausibility and their putative role in IBD carcinogenesis. Polyadenylated mRNA (PolyA(+) mRNA) preparation from inflamed intestinal mucosa of patient s with a longstanding history of UC and CD was performed with subsequent hy bridization of cc phosphorus [alpha-(32)p]-deoxyadenotriphosphate-labeled c omplementary deoxyribonucleic acid (DNA) populations to nucleic acid arrays . Of 588 different human gene transcripts arrayed, secreted apoptosis-relat ed protein 1 (Sarp1), frizzled (fz) homologues, and disheveled (dvl) were d ifferentially expressed, being elevated in UC as compared to CD. These gene s encode proteins involved in the Wingless-type (Wnt)/ beta -catenin signal ing pathway. The autonomous expression of Sarp1 and Sarp1-compatible fz rec eptor genes suggests that the Wnt pathway may be involved in UC carcinogene sis.