Clinical and functional characterisation of novel gene candidates for colorectal cancer
Document TypePhD thesis
Access StatusOpen Access
© 2018 Dr. Marie Parsons
Colorectal cancer (CRC) is the third most common cancer worldwide, affecting over 15,000 individuals in Australia each year. While CRC is often detected at a stage where resection of the primary tumour is possible, approximately 50% will relapse and die from metastatic disease. Current practice to determine clinical management and prognosis is determined by tumour depth (T) and lymph node stage (N) and the extent of cancer spread at diagnosis (M) (TNM staging). However, clinical outcomes of patients with the same TNM staging can be heterogeneous. While adjuvant 5-flurorouracil (5-FU) based chemotherapy is offered to the majority of patients with stage III CRC it is only offered for high risk stage II CRC and many will relapse to 5-FU as a first line therapy. Therefore, there is a need to identify markers to better predict prognosis and better stratify patients with stage II/III CRC for treatment regimes. Currently, the use of biomarkers in prognostication for the management of CRC is still not common practice with only a few markers used in the clinic. The mutational landscape of CRC has revealed large numbers of mutated genes; however, it is not known which are drivers that contribute to carcinogenesis and whether such mutations provide prognostic information. This thesis aims to (I) identify clinically relevant markers and patient subgroups of CRC to better predict prognosis and better stratify patients with stage II/III CRC for treatment regimes, (II) to investigate the potential for a MACROD2 deletion as a novel driver of CRC tumourigenesis and (III) to elucidate the impact of a MACROD2 gene deletion on DNA repair and chromosomal instability in CRC.
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