Abstract
Bladder cancer is the 9th common cancer in the world and the most common malignancy among Egyptian males. The two main types of bladder cancer are SCC and TCC. SCC is more common in developing countries while TCC is more common in developed countries. It is well known that SCC is attributed to Schistosoma haematobium infection. Risk factors for the development of bladder cancer also include genetic-and-molecular abnormalities, chemical, environmental exposures and chronic irritation. One approach to the study of cancer is the determination of Loss-of-heterozygosity since this may be a marker for deletion of a tumour suppressor gene(s). Deletion of some regions on chromosome 8 and or 9 has been investigated among tumour samples by use of microsatellites markers and fragment analysis. The tumour samples were from FFPE archival tissues from Egyptian patients and LoH was estimated at the population level by comparison to normal samples were from buccal mucosa of an ethnically matched group.LoH was found with statistical significance (p value < 0.05) at the locus D8S85 located at 8q22. Frequency of deletion at this locus was 38% and was more correlated to TCC rather than SCC. This is suggestive that there may be a tumour suppressor gene at this region. Screening around this locus on 8q has revealed more regions with deletion with statistical significance. These loci were at D8S267, D8S1045, D8S1008 and D8S497. The highest frequency of deletion among these loci was found at D8S1045 located at 8q22.2 and was 50% and also related to TCC while the frequency was the lowest at D8S521 (18%). At chromosome 9, LoH was had highest frequency at D9S166 located at 9q 12-21 as it was 67.5%. Other loci on 9q also showed high frequency of deletion such as D9S66 (53.4%), D9S60 (30%) and D9S53 (29.1%). LoH at these loci on chromosome 9 was found with statistical significance. No statistical significance was found between LoH at these loci on chromosome 9 and SCC or TCC. LoH is an early event in the progression of bladder cancer as no correlation was found between LoH and the stage of the tumour on either chromosome 8 or 9.
Q-PCR was used as an alternative assessment of the allelic status of tumour samples but the results did not agree with those generated by fragment analysis. This may be suggestive that qPCR is not the best method for evaluation of the allelic status.
| Date of Award | 2010 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | John Craft (Supervisor) & Christopher Bartholomew (Supervisor) |