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A pioneering study, led by UK universities, including the University of Oxford, The Institute of Cancer Research, London, the University of Manchester and the University of Leeds, has provided the most comprehensive analysis to date of the genetic makeup of colorectal cancer (CRC).

Cancers develop partly through genetic abnormalities within cells of the body. Colorectal cancer is a major cause of death worldwide, but we don’t yet have a full understanding of the genetic changes that cause it to grow. New research, published today in Nature, delivers an unprecedented view of the genetic landscape of CRC and its responses to treatment.

Utilising data from 2,023 bowel cancers from the 100,000 Genomes Project led by Genomics England and NHS England, the research team has identified new gene faults that lead to CRC. They’ve also uncovered new CRC cancer sub-groups (categories of cancer with specific genetic characteristics that affect how cancer behaves and responds to treatment). These findings offer profound insights into the disease's development and potential treatment strategies.

Key Findings: 

    • Identification of Over 250 Key Genes: The study has pinpointed more than 250 genes that play a crucial role in CRC, the great majority of which have not been previously linked to CRC or other cancers, expanding our understanding of how CRC develops.
    • New Sub-Groups of CRC: Four novel, common sub-groups of CRC have been discovered based on genetic features. In addition, several rare CRC sub-groups have been identified and characterised. These groups have different patient outcomes and may respond differently to therapy.
    • Genetic Mutation Causes: The research reveals a variety of genetic changes across different regions of the colorectum, highlighting differences in CRC causes between individuals. For example, a process has been found that is more active in younger CRC patients’ cancers; the cause is unknown, but might be linked to diet and smoking.

Commenting on the findings, co-lead researcher, Ian Tomlinson, Professor of Cancer Genetics at the University of Oxford, said:

 Our findings represent a significant advancement in understanding colorectal cancer. By better understanding the genetic changes in CRC, we can better predict patient outcomes and identify new treatment strategies, quite possibly including the use of anti-cancer drugs that are not currently used for CRC."

The research provides a vital resource for the scientific community and a promising foundation for future studies. The results from the study are available to other researchers, who are invited to build on the data by undertaking more focussed projects based on the CRC genome.

The research team spanned the Universities of Oxford, Manchester, Birmingham, Edinburgh and Leeds, as well as The Institute of Cancer Research, London and the Centro de Investigación Biomédica en Red Cáncer, Barcelona.  

**The 100,000 Genomes Project is an ambitious initiative that sequenced 100,000 genomes from NHS patients affected by rare conditions or cancer, providing both diagnoses and access to treatment for thousands of patients with research and analysis still ongoing. The Project laid the foundations for the NHS to become the first national health system to offer whole genome sequencing as part of routine care via the NHS Genomic Medicine Service. 

Read the full paper in Nature here.

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