Tumour Formation PDF

How do cancer mutations affect tumour formation? Luke Boulter MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine  Objective 1: to understand that cancers are not genetically simple, but arise from a multi step process Objective 2: demonstrate that cancer mutations affect t...

How do cancer mutations affect tumour formation? Luke Boulter MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine  Objective 1: to understand that cancers are not genetically simple, but arise from a multi step process Objective 2: demonstrate that cancer mutations affect the tumour micro environment and how a tumour forms. Do Cancers form in a cell autonomous way? Conclusions 1. Tumours are complex pathological organs that have a huge level of genetic complexity – and whilst a single tumour can pathologically look the same, it can be made up of many different clones and sub clones that have different genetics. 2. Tumours evolve over time and this diversification drives therapeutic resistance and metastasis. 3. Cancer cells are part of a complex tumour, that has a vascular microenvironment, stroma and immune system. So why should we seek to understand cancer mutations? We are interested in the recurrent signals and processes that are needed for ducts to grow Cholangiocarcinoma – cancer of the bile duct Key Facts: Second most common cause of primary liver cancer accounting for 40% of deaths from primary liver cancer in 2018. Normally asymptomatic until disease is advanced. Presents as oligo metastatic disease Only ~30% of patients are operable and of those ~70% relapse 90% mortality in 12 months following diagnosis. Limited treatment options Can we identify which mutations are important in cholangiocarcinoma progression? We can use genome sequencing to find which mutations occur in cholangiocarcinoma Too many choices come out of a screen… Recommended Reading: Clonal Heterogeneity and Tumor Evolution: Past, Present, and the Future Nicholas McGranahan and Charles Swanton. 168, volume 168, pg613-628 (2017) Evolution of the cancer genome. Lucy R. Yates & Peter J. Campbell Nature Reviews Genetics volume 13, pg 795–806 (2012 Microenvironmental regulation of tumour angiogenesis: Michele De Palma1, Daniela Biziato and Tatiana V. Petrova Nature Reviews Cancer volume 17, pages457–474(2017) How the ageing microenvironment influences tumour progression. Mitchell Fane & Ashani T. Weeraratna. Nature Reviews Cancer volume 20, pages89–106(2020)