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Telomeres as contributing factors of genome instability in oral squamous cell carcinomas

dc.contributor.advisorPopović, Branka
dc.contributor.otherBabić, Marko
dc.contributor.otherPetrović, Milan
dc.contributor.otherRadojević-Škodrić, Sanja
dc.creatorČarkić, Jelena M.
dc.date.accessioned2017-03-18T19:49:15Z
dc.date.available2017-03-18T19:49:15Z
dc.date.issued2016-09-23
dc.identifier.urihttp://eteze.bg.ac.rs/application/showtheses?thesesId=4679
dc.identifier.urihttps://fedorabg.bg.ac.rs/fedora/get/o:14871/bdef:Content/download
dc.identifier.urihttp://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=48770575
dc.identifier.urihttp://nardus.mpn.gov.rs/123456789/7722
dc.description.abstractUvod. Oralni planocelularni karcinom (OPCK) karakteriše se visokom incidencom i niskom stopom preživljavanja, što ukazuje na neophodnost pronalaženja novih dijagnostičkih i terapijskih markera. U poslednjoj deceniji, pored analize mutacionog statusa oralnih karcinoma, sve veći značaj se pridaje i naslednoj predispoziciji kao faktoru rizika za razvoj ovog tipa maligniteta. Generalno, oralna patogeneza je posledica progresivne genomske nestabilnosti, a koja je jednim delom određena i dužinom telomera i nivoom aktivnosti telomeraze. Telomere su nukleoproteinske strukture lokalizovane na krajevima hromozoma, koje se skraćuju određenom stopom sa ćelijskim deobama, dok se ne dostigne određena kritična dužina koja ili onemogućava dalje deobe i uvodi ćeliju u replikativno starenje i apoptozu, ili dovodi do sticanja sposobnosti neograničenih deoba zahvaljujući aktivnosti telomeraze. Enzim telomeraza predstavlja ribonukleoproteinski kompleks izgrađen od proteinske subjedinice i RNK matrice (TR), čija je uloga sinteza telomernih ponovaka. Istraživanja pokazuju da značajnu ulogu u modulaciji aktivnosti telomeraze imaju polimorfizmi pojedinačnih nukleotida (SNP) u TERT-CLPTM1L genskom regionu-5p.15.33. U okviru ovog lokusa nalazi se TERT gen koji kodira katalitičku subjedinicu telomeraze i gen za CLPTM1L protein koji je uključen u proces apoptoze. Polimorfizmi ovih gena su u brojnim studijama asocijacije dovedeni u vezu sa rizikom od različitih tipova kancera, uključujući i OPCK. Takođe, s obzirom na blisku lokalizaciju često pokazuju visok nivo gametske neravnoteže vezanosti (LD). Cilj. Cilj ove doktorske disertacije bio je ispitivanje asocijacije TERT-CLPTM1L polimorfizama sa rizikom od OPCK, kao i odnosa između analiziranih polimorfizama, relativne dužine telomera, ekspresije telomeraze i kliničko-patoloških karakteristika OPCK. Materijal i metode. Studijska grupa obuhvatila je 93 pacijenta sa dijagnostikovanim OPCK i 100 zdravih osoba...sr
dc.description.abstractIntroduction. High incidence and low survival rate of oral squamous cell carcinoma (OSCC) indicate the importance of finding new diagnostic and therapeutical markers for this disease. Apart from mutational analyses, in recent years greater emphasis is placed on hereditary factors as risk contributors. Generaly, oral cancerogenesis occurs as a result of progressive genome instability which is partly defined by telomere length and telomerase activity. Telomeres are nucleoprotein structures localized at the ends of the chromozomes, shortening with each cell division untill threshold lenght is reached and the cells either undergo replicative senescence and apoptosis, or achieve immortality due to the activation of telomerase. The enzyme telomerase is a ribonucleoprotein complex consisting of protein component and RNA component (TR), with a role in compensating telomere attrition. Studies implicate Single Nucleotide Polymorphisms (SNPs) of TERT-CLPTM1L 5p.15.33 gene locus as very important modulators of telomerase activity. This locus contains TERT gene encoding the catalytic subunit of telomerase, and gene for CLPTM1L protein, involved in the process of apoptosis. Cancer GWAS have shown that SNPs of 5p15.33 locus are associated with risk of many types of malignancies, including OSCC. Due to their close localization, SNPs of these genes are often in strong Linkage Disequilibrium (LD). Aim. The aim of this disertation was the assesment of TERT-CLPTM1L polymorphisms as risk factors for OSCC development, and investigation of the relationship between analyzed polymorphisms, relative telomere length (RTL), telomerase expression and clinicopathological characteristics of OSCC. Materials and Methods. Study group incuded 93 patients with OSCC and 100 cancer free controles. Genome DNA was isolated from formalin-fixed, paraffin-embedded (FFPE) tissues in OSCC group and from buccal swabs in control group. Genotyping of polymorphisms was performed using PCR-RFLP method, relative telomere length measurement by real-time PCR, and telomerase expression by immunohistochemistry...en
dc.formatapplication/pdf
dc.languagesr
dc.publisherУниверзитет у Београду, Стоматолошки факултетsr
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/175075/RS//
dc.rightsAutorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)
dc.sourceУниверзитет у Београдуsr
dc.subjectoralni planocelularni karcinom, TERT-CLPTM1L polimorfizmi, dužina telomera, telomerazasr
dc.subjectoral squamous cell carcinoma, TERT-CLPTM1L polymorphisms, telomere length, telomeraseen
dc.titleTelomere kao faktor genomske nestabilnosti kod oralnih planocelularnih karcinomasr
dc.title.alternativeTelomeres as contributing factors of genome instability in oral squamous cell carcinomasen
dc.typePhD thesis
dcterms.abstractПоповић, Бранка; Бабић, Марко; Петровић, Милан; Радојевић-Шкодрић, Сања; Чаркић, Јелена М.; Теломере као фактор геномске нестабилности код оралних планоцелуларних карцинома; Теломере као фактор геномске нестабилности код оралних планоцелуларних карцинома;


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