Genetic and epigenetic alterations in cholangiocarcinoma

Number of common DMRs in 18 CC cases and overlaps with presumed micro RNA promoter regions.
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Cholangiocarcinoma (CC) is a rare malignant tumor of the bile duct with frequently fatal outcome due to late diagnosis. While CC can be often traced to liver-fluke infections in south-eastern Asia, its etiology in the Western world is largely elusive. Recurrent mutations are rare in CC, raising suspicion of epigenetic changes contributing to onset and progression of the disease. In collaboration with the Institute of Pathology of the University Clinic Heidelberg (Prof. P. Schirmacher, Dr. B. Goeppert), we study CC at various levels including the exome, the DNA methylome, non-coding RNAs, protein expression and gene regulation. Differentially methylated regions (DMRs) were found to be associated with cancer-related pathways (Wnt, TGF-β, and PI3K signaling) and aberrant expression of proteinsand micro RNAs. Our studies aim to improve early diagnosis and outcome of CC by the identification of biomarkers for pre-malignant stages and of druggable molecular targets.

 

Publications:

Goeppert B, Konermann C, Schmidt CR, Bogatyrova O, Geiselhart L, Ernst C, Gu L, Becker N, Zucknick M, Mehrabi A, Hafezi M, Klauschen F, Stenzinger A, Warth A, Breuhahn K, Renner M, Weichert W, Schirmacher P, Plass C, Weichenhan D. Global alterations of DNA methylation in cholangiocarcinoma target the Wnt signaling pathway. Hepatology 2014; 59: 544-554. Abstract

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