رسالة جامعية
Πολυμορφικοί δείκτες και χρωμοσωμικές θραύσεις στην καρκινογένεση ; A study of chromosomal breaks in carcinogenesis using polymorphic markers
| العنوان: | Πολυμορφικοί δείκτες και χρωμοσωμικές θραύσεις στην καρκινογένεση ; A study of chromosomal breaks in carcinogenesis using polymorphic markers |
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| المؤلفون: | Tsantoulis, Petros, Τσαντούλης, Πέτρος |
| بيانات النشر: | National and Kapodistrian University of Athens Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ) |
| سنة النشر: | 2007 |
| المجموعة: | National Archive of PhD Theses (National Documentation Centre Greece) |
| مصطلحات موضوعية: | Καρκινογένεση, Εύθραστες θέσεις, Μικροσυστοιχίες DNA, Ευκαμψία, Επαναλαμβανόμενο DNA, Carcinogenesis, Fragile sites, DNA microarrays, Flexibility, Repetitive DNA, Ιατρική και Επιστήμες Υγείας, Βασική Ιατρική, Medical and Health Sciences, Basic Medicine |
| الوصف: | Introduction. Recent studies have implicated the DNA damage response pathway in the earliest stages of carcinogenesis. It appears that fragile sites may be particularly vulnerable (for example, FRA3B, FRA9E, FRA11C) leading us and others to hypothesize that they may be preferentially targeted even in early lesions. Methods. The experimental material, human and mouse genomic DNA, was derived from two experimental models of carcinogenesis: human skin xenografts that were grown with the addition of exogenous growth factors and urothelial hyperplasia from transgenic mice overexpressing the RAS gene. The development of the material recapitulates the pathological course of preneoplastic lesions and represents its earliest stages with accuracy. In addition, we also analysed DNA from U2OS cells that were grown under replication stress, induced by the overexpression of the CDT1 gene. We employed state-of-the-art DNA microarray technology (Affymetrix SNP and Nimblegen aCGH) in order to evaluate at once up to 10204 positions on the human genome and 385000 positions on the mouse genome. The juxtaposition of normal and abnormal counterparts enabled us to precisely locate genomic lesions, especially loss-of-heterozygosity (hemizygous deletion). We analyzed the human genome project release 36.1, including the assembled chromosomes and the corresponding annotation which were obtained from NCBI. Based on a previous, well known algorithm (FLEX-STAB software, first presented by Mishmar et al, 1999), we devised and implemented a novel method to study the structural characteristics of DNA sequences. Using Repeat Masker we estimated the presence of repetitive DNA within normal and fragile regions. In total, we analysed approximately 2.5 billion bases, divided into 56 common fragile sites (aphidicolin type) and 1913 non-fragile chromosome bands. Results and conclusions. The percentage of LOH was 13.53% (28 of 189 SNPs) in fragile sites and 9.4% in non-fragile sites (logistic regression, p = 0.04). Out of 44 fragile sites that ... |
| نوع الوثيقة: | doctoral or postdoctoral thesis |
| اللغة: | Greek, Modern (1453-) |
| العلاقة: | http://hdl.handle.net/10442/hedi/24715Test |
| DOI: | 10.12681/eadd/24715 |
| الإتاحة: | https://doi.org/10.12681/eadd/24715Test http://hdl.handle.net/10442/hedi/24715Test |
| رقم الانضمام: | edsbas.E14AAD3A |
| قاعدة البيانات: | BASE |
| DOI: | 10.12681/eadd/24715 |
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