Doctoral theses
Current Record: 2152 of 2443
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| Identifier |
uch.med.phd//2001rizos |
| Title |
Μελέτη των γενετικών αλλοιώσεων σε όγκους λάρυγγος ληφθέντων με λαρυγγοσκόπιο |
| Creator |
Rizos, Emmanouel N
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| Abstract |
Laryngeal cancer is a rare type of neoplasia constituting approximately 2% of all human cancers (mainly are squamous cell carcinomas) with a considerable geographical variation of the disease. Tobacco and alcohol abuse seem to be closely related to laryngeal cancer. The activation of oncogenes and the inactivation of tumour suppressor genes, play a critical role in laryngeal tumourigenesis. Recent investigations revealed that 8p, 9p and 17q arms of human chromosomes harbour tumour suppressor genes (TSGs), such as p16 and BRCA1, with an important role in the multistage carcinogenesis of the larynx. In order to investigate the implication of these novel TSGs in the development of laryngeal neoplasia, we performed a loss of heterozygosity (LOH) analysis using a bank of 15 polymorphic microsatellite markers (4 at 8p21, 7 at 9p21 and 4 at 17q arm surrounding the BRCA1 region) in a series of 32 laryngeal cytological specimens. (19 squamous cell carcinoma, 13 benign lesions of the larynx). Loss of heterozygosity at 8p, 9p and 17q was found in 47, 78 and 56% of the informative cases, respectively, providing evidence that these genetic loci may be implicated in the development of both benign and malignant laryngeal neoplasms. The phenomenon of microsatellite instability with at least one microsatellite marker, was found in only two of the 32 specimens tested. Alterations of the genetic loci can be detected, not only in solid tumours of the larynx, but also in cytological specimens suggesting that microsatellite analysis may be a useful tool in the primary diagnosis of the disease. Oncogenes are involved in a wide range of human tumours including laryngeal tumours. Mutations of the ras gene family is one of the main activating mechanisms in human cancers. Their involvement in head and neck cancer has been mainly demonstrated at the level of overexpression. The rate of ras gene mutation has been reported as 4 to 14% in head and neck carcinomas but in squamous cell carcinoma of the head and neck it is less than 5% in the Western World. In the present study, we analysed 41 laryngeal cytological specimens (19 benign and 22 malignant lessions) for mutation in codon 12 of H-, K- and N-ras genes. We employed a non radioactive PCR based method for our analysis. Only 2 point mutations in K-ras (4.8%) and none in the H- and N-ras genes were detected, suggesting that ras mutations are a relatively rare phenomenon in laryngeal tumours. More studies are required, with a large number of samples, for the detection of hot spots for mutations within the non-coding regions of the ras family genes providing clues for their role in the development of laryngeal lesions. In conclusion it was found that: 1) There is a high incidence of loss of heterozygosity at 8p, 9p and 17q in studied laryngeal cytological specimens. 2) There is a low incidence of microsatellite instability in studied laryngeal cytological specimens. 3) There is a low incidence of H-, K- and N-ras oncogene mutations in studied cytological specimens of laryngeal tumours.
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| Issue date |
2001-05-01 |
| Date available |
2001-09-10 |
| Collection
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School/Department--School of Medicine--Department of Medicine--Doctoral theses
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Type of Work--Doctoral theses
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| Permanent Link |
https://elocus.lib.uoc.gr//dlib/c/e/3/metadata-dlib-2001rizos.tkl
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| Views |
317 |
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