Aneuploidy-Associated Gene Expression Signatures Characterize Malignant Transformation in Ulcerative Colitis

• DOI: 10.1097/mib.0b013e31827eeaa4
• Publication Date: 2013-03-02T04:54:57Z
• Authors: Marco Gerling; Kari Nousiainen; Sampsa Hautaniemi; Stefan Krüger; Britta Fritzsche; Nils Homann; Hans-Peter Bruch; Gert Auer; Uwe J. Roblick; Thomas Ried; Jens K. Habermann
• Keywords: Malignant Transformation; Chromosome instability

Malignant transformation in ulcerative colitis (UC) is associated with pronounced chromosomal instability, reflected by aneuploidy. Although aneuploidy can precede primary cancer diagnosis UC for more than a decade, little known of its cellular consequences. Whole-genome gene expression analysis was applied to noninflamed colon mucosa, mucosal biopsies patients UC, and UC-associated carcinomas (UCCs). DNA image cytometry used stratify samples into ploidy types. Differentially expressed genes (DEGs) were analyzed Ingenuity Pathway Analysis validated real-time quantitative PCR. Gene changes between normal mucosa (2587 DEGs) UCC (827 DEGs). Cytometry identified euploid or aneuploid biopsies, whereas all UCCs aneuploid. However, 1749 DEGs distinguished UCCs, only 15 differentiated UCCs. A total 16 differentially throughout the whole sequence from controls Particularly, pivotal chromosome segregation (e.g., SMC3 NUF2) regulated along development. The high number dominated inflammatory-associated genes. Subsequent acquisition leads subtle but distinct transcriptional alterations, revealing novel target that drive genomic instability thus carcinogenesis. signature malignant phenotypes suggests these lesions might need be considered as severe high-grade dysplasia.