Epigenetic prognostic biomarkers in colorectal cancer

Benard, Anne (2015)

Doctoral Thesis

Colorectal cancer is one of the most common diagnosed cancers worldwide, and is the second most important cause of cancer mortality in Europe. The current TNM staging system used at the time of diagnosis is insufficient, as patients with the same tumor stage show wide variations in survival and tumor recurrence. Therefore, there is a need for identification of new biomarkers in colorectal cancer in order to identify high-risk patients and to guide treatment decision-making. In this thesis, epigenetic markers, including DNA methylation and histone modifications were studied in colorectal cancer patients. Several epigenetic clinically prognostic biomarkers were identified in colorectal cancer in this thesis, including both genome-wide and gene-specific patterns of DNA methylation and histone modifications. Knowledge of tumor biology is of key importance in the development of new therapies and the making of informed treatment decisions. Pathway-focused approaches, as presented in this thesis, provide information regarding possible synergistic interactions of biomarkers. Epigenetic mechanisms are unquestionably tied to the tumorigenic process and should be considered as a grand new source of information not only for identification of prognostic and predictive biomarkers, but also for the development of new, possibly tumor- and therefore patient-specific, anti-cancer therapies.

• Prognosis
• DNA methylation
• Histone modifications
• Recurrence
• Survival
• Colorectal cancer
• Epigenetics

• All authors: Benard, Anne
• Supervisor: de Velde, C.J.H. van
• Co-supervisor: Kuppen, P.J.K.
• Qualification: Doctor (dr.)
• Awarding Institution: Leiden University Medical Center (LUMC), Leiden University
• Date: 2015-04-21
• ISBN (print): 9789462595637