A cell type specific DNA methylation atlas to study health and disease

Gene expression control is fundamental to our understanding of human development and disease. DNA methylation is a well-studied modification of DNA playing a key role in the regulation of gene-expression, and changes in DNA methylation are often associated with cancer and cancer progression. For this project experts in gene regulation (Gribnau), cancer research (Martens, Wilting) and pathology (van Kemenade) team up with experts in DNA methylation assay development (Methylomics B.V.) to establish DNA methylation maps of relevant cell types in the body, that will serve as a reference to study cancer progression and treatment outcome.

The team will focus on colon and cervical cancer that rank among the top ten causes of cancer-related mortality. In the Netherlands population screening programmes have been implemented nationally to identify cancer at an early stage, among them programmes for cervical- and colorectal cancer. At present, assays to detect these forms of cancer are costly and labour intensive, and therefore alternative molecular assays with a high sensitivity and specificity are needed.

The team of experts will develop new technologies and assays to extract DNA methylation profiles from all relevant cell types. At the end of this project a DNA methylation atlas of all cell types of the colorectal and uro-genital zones will be developed that will then serve as a reference to study cancer progression, treatment response and to identify the origin of cancer. These new insights will then be applied to develop high-throughput, low cost, PCR based assays for cancer (progression) detection.

Gene expression control is fundamental to our understanding of human development and disease. DNA methylation is a well-studied modification of DNA playing a key role in the regulation of gene-expression, and changes in DNA methylation are often associated with cancer and cancer progression. For this project experts in gene regulation (Gribnau), cancer research (Martens, Wilting) and pathology (van Kemenade) have teamed up with experts in DNA methylation assay development (Methylomics B.V.) to establish DNA methylation maps of relevant cell types in the body, that served as a reference to study cancer progression and treatment outcome. The team focused on colon and cervical cancer that rank among the top ten causes of cancer-related mortality. In the Netherlands population screening programs have been implemented nationally to identify cancer at an early stage, among them programs for cervical- and colorectal cancer. The team developed new technologies and assays to extract DNA methylation profiles from all relevant cell types. Among the realized deliverables are a novel technology to generate genome-wide DNA methylation profiles of single cells, the application of MeD-seq for DNA methylation profiling of cell free DNA, and PCR based assays for cancer detection. In follow-up projects we will validate our assays for clinical application in disease detection and treatment monitoring.