Early detection of colorectal cancer
CRC has a high prevalence in both males and females, and it is perhaps the best understood of all epithelial tumours in terms of its molecular origin. Yet, the full complement of molecular lesions necessary to cause CRC is poorly understood. The goal of the EU-funded SYSCOL (Systems biology of colorectal cancer) project was to develop methods and tools that enable a better understanding of the gene regulatory systems underlying the disease. The experimental part of the study entailed generation of DNA and RNA sequence data from patient samples and epigenetic modification analysis. Collectively, this work aimed to identify mutations and polymorphisms that affect cancer risk and delineate the mechanisms that drive CRC formation. Project partners identified five novel variants that increase an individual's risk of developing CRC. Three of the variants are common, but only involve a small risk. Two variants are rare, but individuals carrying them have a high risk of developing CRC. Early detection by screening would therefore be of great importance for identifying high-risk patients. The collaborative work also resulted in the discovery of an important gene switch that promotes CRC. This genetic variant is very common and therefore accounts for more inherited cancer than any other currently known genetic variant or mutation. Another important advance was the development of an approach for detecting cancer DNA in the blood. The use of such a non-invasive method to detect tumours in patients could greatly improve clinical management. An interesting aspect of SYSCOL's work regarding fundamental understanding of the genome of cancer cells was the finding that only a small fraction of a CRC cell's genome is involved in gene expression regulation. This challenges current ideas about the genomic complexity of cancer. The huge amount of patient-derived molecular and clinical data generated and integrated into the CRC model significantly increases understanding of the mechanisms behind CRC. This model can be used to find novel, druggable therapeutic targets that will have a long-term impact on human health. Systems biology tools and computational models developed within the project have resulted in a better understanding of the complex network of genes and regulatory systems behind CRC. Furthermore, the methods and tools developed and shared via the SYSCOL website may be applied to the study of other complex disorders, with implications for research, prevention and treatment.
Keywords
Colorectal cancer, systems biology, SYSCOL, gene regulatory system, epigenetic
