Research Our PhDs Mutation in the BRAF gene in colorectal cancer The team will generate organoids (mini versions of the gut derived from stem cells) to analyse atypical BRAF mutations and determine how these work within a wider RAS pathway (another set of gene interactions) to drive the development of colorectal cancer. They will use pairs of organoids representing rectum and caecum to look further into very specific condon mutations that are implicated particularly in rectal cancer. Finally, they will examine the relationship between atypical BRAF mutations and the prognosis for patients, and will screen drugs that target the wider RAS pathway to see what effect they may have against these BRAF mutations. What is a genetic pathway? A gene regulatory pathway turns genes on or off. This essentially means that the processes happening in the pathway control the function of the genes. What is a genetic mutation? A mutation is a change in a DNA sequence. Mutations can be caused by mistakes during cell division, ionizing radiation, certain chemicals and viruses. The researchers This PhD study is being led by Professor Ian Tomlinson, Director of the Institute of Cancer and Genomic Sciences at the University of Birmingham in collaboration with Dr Andrew Beggs, a consultant colorectal surgeon and major contributor to the Human Cancer Model Initiative. Why study BRAF mutations in colorectal cancer? BRAF genes are among those known as oncogenes. These are genes which, when mutated, lead to the development of cancer. Treatments have been developed that are effective against this mutation in lung cancer and melanoma, but not in colorectal cancer. Additionally atypical BRAF mutations that drive rectal cancer have received very little attention in terms of research, while the majority of colorectal cancers occur in the rectum (around 20,000 each year). This study will make an important contribution to our knowledge about this type of mutation and should lead onto further work to develop effective therapies. This study was made possible through the fundraising and donations of the family and friends of Lucy Thomas, who died of a rare form of bowel and liver cancer in April 2017.