Tumourigenesis is driven by genetic alterations and by changes in the epigenome, for instance by the addition of methyl groups to cytosine bases in the DNA. A deeper understanding of the interaction between the genetic and epigenetic mechanisms is critical for the selection of tumour biomarkers and for the future development of therapies. Human tumour specimens and cell lines however contain a plethora of genetic and epigenetic changes, which complicate data analysis. In contrast, certain mouse tumour models contain only a single genetic mutation and allow the analysis of nascent tumours. Scientists of the Max Planck Institute for Molecular Genetics in Berlin have now discovered a recurring pattern of more than 13,000 epigenetic alterations in young tumours of the mouse. This genome-wide pattern was found to be partly conserved in human colon carcinoma, and may therefor facilitate the identification of novel clinical colon cancer biomarkers for early detection.
Two kinds of molecular changes are known to trigger tumour development: one is genetic mutations - i.e. alterations in the alphabetic sequence of the DNA -activating genes that lead to uncontrolled growth of tumours, or inactivating genes that inhibit this growth. The other is epigenetic modifications, for example new distributions of methyl groups in the DNA that contribute to the genetic information in the cancer cells being interpreted differently.
Genetic and epigenetic mechanisms work together in cancer development - but little was known about how these systems mutually influence one another, and which changes first come to light. These questions can only be answered with great difficulty through investigating human tumours: the cancer is usually already several years old when diagnosed. Accordingly, the cancer cells already exhibit thousands of genetic and epigenetic changes at this stage, which complicates the analysis.
The matter is different for the corresponding polyps in mice, which the researchers can investigate considerably earlier following their formation. For this reason, scientists of the Max Planck Institute for Molecular Genetics have now pursued the question of which epigenetic changes in intestinal tumours occur first with the help of a mouse model.