21DSG10
Doctoral Thesis
Project commenced:Morgan Jones (Ngāi Tahu), The University of Otago
The heterogenic nature of cancer and the ability for cancers to undergo metastasis has presented researchers with a major hurdle towards finding a cure or preventive measures for cancer development. Although cancer metastasis is the main cause of cancer-related deaths, the underlying mechanisms or mutational events that cause metastasis have not been identified.
Cell free DNA (cfDNA) in human body fluids is made up of short DNA fragments around 160-180bp; results from recent studies suggest that tumour derived cfDNA, termed circulating tumour DNA (ctDNA) is present in the blood of cancer patients. DNA methylation changes occur early during tumorigenesis and metastasis and are present throughout the entire cancer process, thus suggesting that methylation pattern analysis of ctDNA may provide a robust and achievable approach for identifying the likely presence of secondary tumours and finding predictor markers of cancer metastasis.
Our first objective will involve developing a standardised method which we can use to analyse ctDNA from cancer patient plasma samples using whole genome bisulfite sequencing (WGBS) and an adapted version of single-cell reduced-representation bisulfite sequencing (scRRBS). Following this we will attempt to identify potential epigenetic markers, drivers or mechanisms of colorectal cancer metastasis by comparing matched primary and secondary tissues along with analyzing genomes from global databases.