University College London
This PhD project will use new computational approaches to identify where sarcomas have made changes to a person’s DNA and left a footprint (or ‘mutation signature’). Once these footprints can be identified in DNA, they can be used to identify which patients will respond to specific treatment. It will train a researcher of the future in this cutting edge research field.
Utilisation of genomic mutational signatures in sarcoma for clinical benefit
Cancer is a disease caused by mistakes in our DNA (mutations). Factors such as smoking or exposure to dangerous levels of UV light create many thousands of such mutations in the DNA, leaving behind a tell-tale footprint which is helpful in pinpointing the cause.
Recently it has been shown using elegant mathematical and computational approaches that these mutation footprints, also known as mutational signatures can be detected from sequenced DNA. Importantly these signatures can be used to select patients for specific treatments, particularly those that boost the immune system to fight cancer and can help predict the outcome of the disease. This has been shown in colorectal, ovarian and some other common cancers.
Sarcomas are different to many common cancers in that they have very complex mutations. Large pieces of DNA are lost, gained or even rearranged in multiple ways requiring the development of new computational approaches to identify these type of signatures. The student will work with experts in the field of cancer genomics in UCL and collaborate with researchers from the Francis Crick Institute, Wellcome Trust Sanger Institute and University of California San Diego. Carrying out such work for sarcoma patients will be beneficial as these methods can then be applied to the data that is being produced from sarcoma patients that are enrolled in the national 100,000 genomes project and beyond.