Colorectal cancer is one of the most common cancer types worldwide and a major contributor to cancer related deaths. In the Lind lab, we are working with epigenetic alterations in colorectal cancer, focusing on DNA methylation aberrations as potential biomarkers.

Liquid biopsies:

DNA methylation biomarkers in circulating cell-free tumor DNA (ctDNA) in blood have great clinical potential for cancer management. Detection of such aberrations in ctDNA is, however, challenging and places a great demand on methodology. In the Lind lab we have evaluated several commercial kits for isolation and bisulfite conversion of ctDNA from blood, and identified the best kit combination which gave the highest yield of bisulfite converted cfNDA from plasma (Kresse et al., Clin Epigenetics 2023).

Epigenetic phenotypes in colorectal tumors: CIMP and supernegative tumors

A subset of colorectal tumors (15-20%) displays CpG island methylator phenotype (CIMP), and is characterized by a high level of genes with promoter DNA methylation. We have shown that patients with CIMP tumors have a poor prognosis, which is particularly evident within specific patient subgroups (Vedeld HM et al., Int J Cancer 2017).

By analyzing 2-4 multiregional samples from patients with colorectal cancer, we have further shown that CIMP status is highly homogenous within primary colorectal cancers, but that the methylation status of the individual CIMP markers varies among CIMP positive tumors (Flatin, BTB et al., Int J Cancer 2021).

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 (reduced representation bisulfite sequencing (RRBS) and whole-genome bisulfite sequencing (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 super-negative CRC patients may have a better prognosis than the rest of the CRC patients.

Early detection

Earlier detection has the potential to significantly improve patient survival. In collaboration with the Lothe group, we have identified 12 promising DNA methylation biomarkers for early detection of colorectal cancer. The markers were licensed to Oxford Gene Technologies for further development into a liquid-biopsy-based test for early detection of colorectal cancer. 

Relevant publications:

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