Doctoral theses
Current Record: 2056 of 2435
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| Identifier |
39606 |
| Title |
Γενετική ανάλυση της αλληλουχίας μικροδορυφορικού DNA σε δερματικές νεοπλασματικές αλλοιώσεις |
| Creator |
Saridaki, Zacharenia G
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| Abstract |
Cancer cells are defined by two heritable properties: they reproduce in defiance of the normal restraints and they invade and colonize territories normally reserved for other cells. Tumor suppressor genes are a large group of inhibitory genes that participate in carcinogenesis with a non-dominant effect. Non-melanoma skin cancers, squamous cell carcinomas (SCC) and basal cell carcinomas (BCC), are the most common neoplasias of the Caucasian population. In the present PhD thesis we performed an in vitro analysis of the genetic and molecular characteristics of non-melanoma skin tumors and pre-cancerous lesions (BCC, SCC, Bowens Disease) in order to determine the involvement of INK4a-ARF tumor suppressor genes p16INK4a, p15INK4b and p14ARF in the development of sporadic non-melanoma skin cancer of Greek patients. An allelic imbalance analysis (loss of heterozygosity, LOH and microsatellite instability, MI), as well as, a mutational analysis were performed. For chromosome locus 9p21-p22 the overall frequency of BCC LOH reached 60% and it is the highest reported in the international literature. In addition, the LOH frequency found for SCC and Bowens Disease specimens was also high, reaching 52%. 9p LOH appears to be equally involved in both BCC and SCC tumors. MI was rare in both SCC and BCC specimens. Exons 1α, 1β and 2 of the INK4a-ARF locus were screened for mutations. A Val28Gly substitution in exon 1α and a CCC TTT (Ala57Val and Arg58Ter) substitution in exon 2, resulting in an early termination of the amino acid sequence are reported for the first time in two SCCs, the latter being indicative of a combination of a UV radiation-induced mutation and a point mutation. A previously described polymorphism of the p16INK4a gene, Ala148Thr, was also detected in 5 BCC and 1 SCC specimens in an overall allelic frequency of 3.72%. The elevated LOH frequency confined in locus 9p21-p22, as well as the detection of polymorphism in the p16INK4a gene in a proportion of human BCC tumors provide strong evidence of genetic alteration on the given locus. Thus, inactivation of the p16INK4a gene, or of another/others yet unidentified tumor suppressor gene/s located on this chromosome region, probably have involvement in the carcinogenesis of at least some human BCC. The detected mutations combined with the high frequency of 9p LOH found in our SCC tumors imply that inactivation of INK4a-ARF locuss tumor suppressor genes p16INK4a and p14ARF, via allelic loss and/or mutation (possibly UV induced) could play a significant role in non-melanoma skin cancer development, particularly in the more aggressive SCC type.
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| Language |
Greek |
| Issue date |
2002-11-22 |
| Date available |
2003-07-07 |
| 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/b/d/3/metadata-dlib-2002saridaki.tkl
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| Views |
308 |
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