Colorectal cancer (CRC) is one of the most common cancer types worldwide and a major contributor to cancer related deaths. In the Epigenetics group, we are interested in DNA methylation alterations in CRC, including the potential for early detection, improved prognostication and patient stratification.
Earlier detection has the potential to significantly improve patient survival. In collaboration with Lothe’s group, we have identified 12 promising DNA methylation biomarkers for early detection of CRC.
• GE Lind, T Ahlquist, RA Lothe. DNA Hypermethylation of MAL: A Promising Diagnostic Biomarker for Colorectal Tumors. Gastroenterology 2007
• GE Lind, SA Danielsen, T Ahlquist, MA Merok, K Andresen, RI Skotheim, M Hektoen, TO Rognum, GI Meling, G Hoff, M Bretthauer, E Thiis-Evensen, A Nesbakken and RA Lothe. Identification of an epigenetic biomarker panel with high sensitivity and specificity for colorectal cancer and adenomas. Mol Cancer 2011
• GE Lind, C Raiborg, SA Danielsen, TO Rognum, E Thiis-Evensen, G Hoff, A Nesbakken, H Stenmark and RA Lothe. SPG20, a novel biomarker for early detection of colorectal cancer, encodes a regulator of cytokinesis. Oncogene 2011
• D Ahmed, SA Danielsen, TH Aagesen, M Bretthauer, E Thiis-Evensen, G Hoff, TO Rognum, A Nesbakken, RA Lothe and GE Lind. A Tissue-Based Comparative Effectiveness Analysis of Biomarkers for Early Detection of Colorectal Tumors. Clin Transl Gastroenterol 2012
• HM Vedeld, RI Skotheim, RA Lothe, GE Lind. The recently suggested intestinal cancer stem cell marker DCLK1 is an epigenetic biomarker for colorectal cancer. Epigenetics 2014
• HM Vedeld, K Andresen, IA Eilertsen, A Nesbakken, R Seruca, IP Gladhaug, E Thiis-Evensen, TO Rognum, KM Boberg and GE Lind. The novel colorectal cancer biomarkers CDO1, ZSCAN18 and ZNF331 are frequently methylated across gastrointestinal cancers. IJC 2015
Prognosis and stratification
Epigenetic alterations may also contribute to improved prognostication and stratification:
A subset of colorectal tumors (15-20%) display CpG island methylator phenotype (CIMP), and are characterized by a high level of genes with promoter DNA methylation. In a recent study we showed that patients with CIMP tumors had a poor prognosis, which was particularly evident within specific patient subgroups.
The supernegative colorectal tumors represent a new and intriguing subgroup of cancers, which, in stark contrast to CIMP tumors, have unusually little promoter hypermethylation. Using high-throughput sequencing (RRBS and WGBS*), we are investigating the DNA methylation patterns in these tumors. The subgroup may be a source for identifying novel mechanisms of the DNA methylation and demethylation machineries. Preliminary data suggest that supernegative CRC patients may have a better prognosis than the rest of the CRC patients.
*RRBS: reduced representation bisulfite sequencing
*WGBS: whole-genome bisulfite sequencing