Using patient data to study mutations linked to bladder cancer
2022 Summer Studentship winner Emilia Cross studying at the University of York, was awarded £2,769 for her project to help udnerstand mutations causing baldder cancer.
Emilia Cross has one year left of her Masters (Hons) in Biology course at the University of York. Emilia was actively looking for opportunities to expand her bioinformatics experience around cancer research and approached Dr Andrew Mason, a Research Fellow and Proleptic Lecturer in Cancer Informatics within the Biology department. Emilia is particularly interested in cancer research but was struck by the number of animals used in experiments in this area. Bioinformatics is a field of science that combines biology, computer science, mathematics and statistics to collect and analyse large amounts of biological data, for example, data collected from healthy individuals or patients. Her project uses existing human data to look at specific mutations and their link to bladder cancer development.
Uncovering the tissue-specific role of APOBEC mutagenesis in bladder cancer directly from patients.
Bladder cancer is the 10th most common cancer worldwide, with over 20,500 new cases in the UK each year. When caught early, bladder cancer is treatable, and the prognosis is good. However, tumours recur frequently necessitating regular follow-ups, including invasive screening, rendering bladder cancer the most expensive cancer to treat over a patient’s lifetime. Patient 5-year survival is less than 50%, even after radical surgery to remove the entire bladder. Improving our understanding of how bladder cancer develops will help inform better diagnostic tools and treatments in the future.
In her project Emilia is using data from the 100,000 Genomes Project, an initiative ran by Genomics England, that sequenced the whole genomes (mapped out their genetic code) of around 85,000 National Health Service (NHS) patients affected by rare diseases and cancer, to improve knowledge of the role of mutations in these diseases. This project includes the largest cohort of bladder cancer patient genome data to date. Emilia is looking at the locations of particular mutations caused by over activity of a set of anti-viral, mutation-causing enzymes known as ‘APOBEC’. Whilst APOBEC mutations are known to be associated with bladder, and other, cancer development, less is known about why they tend occur in specific locations. Emilia has developed a hypothesis for this and is using the patients’ genomes to look for patterns, and also look for similar, but cancer-specific patterns in other cancer types.
Emilia hopes her project will help replace rodent use in cancer research where the administration of therapies and cancer development undoubtedly causes suffering to the mice used. Rodents do not have a comparable APOBEC response to humans, rendering mouse models of bladder cancer highly non-specific for the study of (non-carcinogen-induced) bladder tumours. A key model currently used in bladder cancer research and drug development rely on the oral administration of the chemical BNN (N-Butyl-N-(4-hydroxybutyl) nitrosamine), a carcinogen found in cigarette smoke and known to cause aggressive bladder cancer in animals, to mice. This use of a carcinogen is not reflective of the mechanisms for the development of bladder cancer in Europe and North America, where over 85% of bladder cancer tumours have been linked to APOBEC-induced mutations. Human data has the potential to provide new and more relevant insights into the disease.
Emilia shares “Working with the 100K Genome cohort has allowed me to use relevant, human data to investigate the mutations involved in the progression of bladder cancer. With the aid of a high-performance computer cluster, I will be able to harness patient data and map the regions of DNA where tumour-specific mutations tend to occur in bladder cancer and investigate how the APOBEC enzyme is implicated in this mutagenesis. I am excited to gain more skills in programming and data analysis while hopefully furthering the understanding of bladder cancer progression, without the use of animals.”Learn more about the summer studentship scheme