Genotype and cell identity in colorectal cancer: experimental modelling of tumour evolution

Please note that this seminar will be recorded. You can join using the following link: Meeting ID: 992 8152 3878 Passcode: 027138 For those outside the UK you can find your local number here:

Contemporary views on colorectal tumour development propose an alternative narrative to Darwinian evolution. This ‘big bang’ theory suggests that most driver mutations are acquired very early during the pre-malignant phase of tumour development and that additional somatic mutations are then subject to neutral evolution thus generating profound intra-tumoral heterogeneity. Further, it has been shown that common somatic driver mutations including KRAS can be found in apparently normal intestinal epithelia. Previous work from our group and others have also shown that cell identity and fate in both normal and malignant tissue is contextual and in a cancer context unrelated to mutational background. Cumulatively, these data indicate that non-genetic mechanisms may drive cancer cell phenotype and tumour progression. We are beginning to explore this hypothesis focussing initially on competitive and co-operative clonal interactions. We are developing complex genetically engineered organoid systems to address these questions and present our work to-date together with relevant background data.