Metiliranost promotora gena imunosnog sustava u tumorima glave i vrata čovjeka

master's thesis

• Title (english): Methylation of immune gene promoters in human head and neck cancer
• Author: Petra Anić
• Mentor: Nina Milutin Gašperov (mentor)
• Mentor: Inga Marijanović (sumentor)
• Committee member: Inga Marijanović (predsjednik povjerenstva)
• Committee member: Ana Galov (član povjerenstva)
• Committee member: Silvija Černi (član povjerenstva)
• Committee member: Mirna Ćurković Perica (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2020-02-20, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Udio tumora glave i vrata koji se mogu povezati s infekcijom humanim papiloma virusima (HPV, Human papilloma virus) raste. Jedan od potencijalnih čimbenika odgovornih za nastanak tumora kod infekcije HPV-om je promjena stupnja metiliranosti promotora gena koji igraju ključnu ulogu u imunosnom odgovoru. U radu je istražena razlika u metiliranosti promotora gena: EDARADD, IL12RB, MARCO, HLA DPB, GBP, SIGLEC i HAVCR2 u obriscima zdrave oralne sluznice naspram svježeg tkiva oralnih i orofarinegealnih tumora čovjeka. Ispitano je i prisustvo infekcije HPV-om u svakom pojedinom uzorku. Za određivanje razlike u metiliranosti promotora navedenih gena, prethodno izolirana DNA je podvrgnuta kemijskoj modifikaciji natrijevim bisulfitom te umnožena metodom lančane reakcije polimerazom specifične za metilaciju. Analizirani geni pokazali su hipometiliranost kod uzoraka oralnih i orofaringealnih tumora glave i vrata u usporedbi s normalnim tkivom. Također, udio nemetiliranih promotora navedenih gena bio je veći kod HPV-pozitivnih tumora nego kod HPV-negativnih tumora, što ukazuje da je njihova aktivacija demetiliranjem najvjerojatnije odgovor na onkogene E6 i E7 HPV-a. Razlike u metiliranosti navedenih gena mogu biti pokazatelji prognoze te progresije pojedinih tumora glave i vrata te, po mogućnosti, odgovor na pitanje zašto kod nekih ljudi dolazi do razvoja ovih tumora, dok kod drugih ne, bez obzira na infekciju HPV-om.

Abstract (english)

The proportion of human head and neck (HNC) cancer that can be attributable to human papilloma virus (HPV) infection is growing. A potential factor responsible for the emergence of HPV-positive HNC is a change in the degree of methylation of gene promoters that play a key role in the immune response. In this study, we investigated the difference in methylation of EDARADD, IL12RB, MARCO, HLA DPB, GBP, SIGLEC and HAVCR2 gene promoters, in samples of healthy oral mucosa versus samples of oral and oropharyngeal tumors. The presence of HPV infection in samples was examined. To determine the difference in methylation of those gene promotors, isolated DNA was subjected to chemical modification by sodium bisulfite and amplified by methylation-specific PCR method. Analyzed genes showed hypomethylation in samples of oral and oropharyngeal tumors compared to normal tissue. Proportion of unmethylated promoters is higher in HPV-positive tumors than in HPV-negative tumors, indicating that their activation by demethylation is most likely a response to HPV oncogenes E6 and E7. These differences may be indicators of the prognosis and the progression of individual HNC and answer to the question why some people develop HNC, while others not, regardless of HPV infection.

• Keywords: oralni i orofaringealni tumori; imunosni sustav; epigenetičke promjene; HPV
• Keywords (english): oral and oropharyngeal tumors; immune system; epigenetic changes; HPV Supervisor: Nina Milutin Gašperov; PhD
• Language: croatian
• URN:NBN: urn:nbn:hr:217:918563
• Study programme: Title: Molecular Biology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra molekularne biologije (magistar/magistra molekularne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access; Embargo expiration date: 2022-02-21
• Created on: 2020-06-09 09:55:12