| Popis: |
More is known about the genes involved in colorectal tumorigenesis than for any other human cancer. Mutations have been identified in many genes, including the K-ras oncogene and the APC, MCC, DC and p53 tumour suppressor genes. However, whilst much is known about these events there are many questions that remain unanswered. Three specific questions involving p53, MCC and APC were addressed in this thesis. Firstly, it has been previously assumed that point mutation of the p53 gene inevitably resulted in a permanently stabilised protein product. To address this question in colorectal carcinomas, the relationship between p53 mutation and stabilisation of p53 protein was assessed by comparing stabilised product detected by immunocytochemistry (ICC) using p53 specific antibodies, with mutation as detected by single strand conformational polymorphism analysis (SSCP) and sequencing. The results suggest a high correlation between p53 protein stabilisation and gene mutation, but highlight specific incidences in which concordance is not absolute. In particular, mutations in exon 6 of p53 did not result in a stabilised protein and several tumours with a high degree of staining contained no apparent mutation within the entire coding region of the gene. Secondly, although MCC (for mutated in colorectal cancer) on chromosome 5q was amongst the first colorectal cancer genes to be identified and was shown to be mutated in a small number of colon tumours, its role is still uncertain. Finally, another gene has also been located on chromosome 5q and had been shown to be mutated in about 60% of sporadic colon tumours as well as in the germline of FPC patients and hence called APC (for adenomatous polyposis coli). |
