Metilacija dna u karcinogenezi

undergraduate thesis

• Title (english): Dna methylation in carcinogenesis
• Author: Una Rastović
• Mentor: Petra Korać (mentor)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2019, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Nastanak karcinoma podrazumijeva inaktivaciju gena za tumorske supresore i aktivaciju
protoonkogena, što za posljedicu ima pojavu obilježja malignih tumora koja uključuju neograničen i
nekontroliran rast i dijeljenje stanica, sposobnost invazije u okolna tkiva, formiranje metastaza te
indukciju angiogeneze. U karcinogenezi osim mutacija u DNA jednak značaj imaju i epigenetički
mehanizmi. U stanju homeostaze u stanici prevladava ravnoteža između metilacije i demetilacije
DNA, dok je u tumorima primijećena globalna hipometilacija genoma te lokalna hipometilacija u
odnosu na neizmijenjene stanice. Lokalna hipermetilacija najčešće se događa u promotorskim
regijama i povezana je s inaktivacijom gena, a globalna hipometilacija doprinosi kromosomskoj
nestabilnosti koja dovodi do kromosomskih rearanžmana koji uključuju aneuploidije, translokacije i
delecije. 5-metilcitozin pospješuje nastanak točkastih mutacija spontanom deaminacijom
posredujući pritom u tranziciji citozina u timin. Osim inaktivacije gena metilacijom, po stanicu je
jednako nepovoljna aktivacija utišanih gena demetilacijom. Na primjerima proteina p16-INK4a,
p14ARF, p53, pVHL i heparanaze prikazana je umreženosti staničnih procesa čiji poremećaji dovode
do nastanka tumora i doprinose malignosti.
Cilj ovog rada bio je prikazati obilježja metilacije DNA i njezin utjecaj na genom te na
primjerima poznatih promjena u statusu metilacije u karcinomima ukazati na važnost metilacije kao
pokretača malignih promjena, ali i na potencijal koji posjeduje za dijagnostičke i terapijske svrhe.

Abstract (english)

Carcinoma development includes tumour suppressor gene inactivation and proto-oncogene
activation which provide the tumour with malignant characteristics such as unlimited and
unregulated cell growth and division, ability to invade surrounding tissues and form mestastasis as
well as to induce angiogenesis. Epigenetic mechanisms in carcinogenesis are equally important as
mutations in DNA. In homeostasis there is a balance between DNA methylation and demethylation
within a cell, while in tumour cells global hypomethilation and local hypermethyilation have been
observed. Local hypermethyilation most commonly affects promoter regions and is associated with
gene inactivation while global hypomethilation contributes to chromosomal instability as it is
associated with chromosomal rearangements which lead to aneuplody, translocations and deletions.
Moreover, 5-methylcytosine increases the rate of point mutations for spontaneous deamination and
causes cytosine to tymine transversions. Both methylation driven gene inactivation and
demethylation of silenced genes represent risk for tumour development. The role of p16-INK4a,
p14ARF, p53, pVHL proteins and heparanase illustrate the complexity of cellular processes whose
dysregulation leads to tumorigenesis and affect the malignancy.
The aim of this work was to show the characteristics of DNA methylation and consequential
effects on the genome, as well as to emphasize the importance of DNA methylation in
carcinogenesis. Using known examples of DNA methylation changes in carcinoma, the aim was to
show its potential as diagnostic and prognostic marker.

• Keywords: metilacija DNA; karcinogeneza
• Language: croatian
• URN:NBN: urn:nbn:hr:217:015523
• Study programme: Title: Molecular Biology; Study programme type: university; Study level: undergraduate; Academic / professional title: sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) molekularne biologije (sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) molekularne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2019-09-17 11:52:15