ABSTRACT
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The molecular mechanisms underlying cancer development have since long been a subject of study. Traditionally, cancer is thought of as a multistep disease, largely based on accumulation of genetic abnormalities, such as amplification, mutations and deletions, leading to gain-of-function of oncogenes, or loss-of-function of tumor suppressor genes [1]. In recent years it has become evident that not only changes at the genomic level but also at the epigenomic level contribute to cancer development. It is now clear that abnormal epigenetic regulation may act as an alternative mechanism for, e.g., loss of tumor suppressor function in cancer cells. One of the best-known examples is the inactivation of tumor suppressor genes, such as p16INK4A and BRCA1, by DNA methylation [2]. In this way, DNA-methylation-dependent gene silencing contributes to biallelic loss of tumor suppressor function, as proposed in the ‘‘two-hit’’ model, by Knudson [3]. Processes or proteins that orchestrate epigenetic regulation may affect expression or regulation of tumor suppressor or oncogenes, and in doing so contribute to tumorigenesis. In this chapter, we specifically focus on a group of epigenetic regulators, the Polycomb group (PcG) proteins and their role in normal development and in tumorigenesis.
