The Annual Meeting of the Finnish collaborative HNPCC reseach groups took place at Hämeenkylän Kartano in Vantaa on 4th of March.
In her presentation, Prof. Minna Nyström introduced DiagMMR™ a new tool for Lynch syndrome carrier diagnosis (http://www.lscancerdiag.com/). Other members of Prof. Päivi Peltomäki’s and Prof. Minna Nyström’s research groups gave presentations regarding some of the recent projects related to the Western diet effects on colon cancer predisposition (MSc. Marjaana Pussila, MSc. Satu Valo and BSc. Pauliina Paloviita) and promoter specific alterations of APC in FAP (PhD Taina Nieminen).
MSc. Satu Valo
PhD. Taina Nieminen
The Role of Chromosomal Instability and Epigenetics in Colorectal Cancers Lacking β-Catenin/TCF Regulated Transcription
Abdel-Rahman WM, Lotsari-Salomaa JE, Kaur S, Niskakoski A, Knuutila S, Järvinen H, Mecklin JP and Peltomäki P.
All colorectal cancer cell lines except RKO displayed active β-catenin/TCF regulated transcription. This feature of RKO was noted in familial colon cancers; hence our aim was to dissect its carcinogenic mechanism. MFISH and CGH revealed distinct instability of chromosome structure in RKO. Gene expression microarray of RKO versus 7 colon cancer lines (with active Wnt signaling) and 3 normal specimens revealed 611 differentially expressed genes. The majority of the tested gene loci were susceptible to LOH in primary tumors with various β-catenin localizations as a surrogate marker for β-catenin activation. The immunohistochemistry of selected genes (IFI16, RGS4, MCTP1, DGKI, OBCAM/OPCML, and GLIPR1) confirmed that they were differentially expressed in clinical specimens. Since epigenetic mechanisms can contribute to expression changes, selected target genes were evaluated for promoter methylation in patient specimens from sporadic and hereditary colorectal cancers. CMTM3, DGKI, and OPCML were frequently hypermethylated in both groups, whereas KLK10, EPCAM, and DLC1 displayed subgroup specificity. The overall fraction of hypermethylated genes was higher in tumors with membranous β-catenin. We identified novel genes in colorectal carcinogenesis that might be useful in personalized tumor profiling. Tumors with inactive Wnt signaling are a heterogeneous group displaying interaction of chromosomal instability, Wnt signaling, and epigenetics.
Gastroenterol Res Pract. 2016