NOTCH2 u meningeomima različitih gradusa: analiza metilacijskog statusa promotora gena i ekspresije proteina

master's thesis

• Title (english): NOTCH2 in different meningeoma grades: protein expression and methylation status analysis
• Author: Božana Blažević
• Mentor: Dubravka Hranilović (mentor)
• Mentor: Anja Bukovac (komentor)
• Committee member: Dubravka Hranilović (predsjednik povjerenstva)
• Committee member: Biljana Balen (član povjerenstva)
• Committee member: Maja Matulić (član povjerenstva)
• Committee member: Sandra Hudina (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2023-02-23, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Meningeomi su najčešći primarni tumori središnjeg živčanog sustava klasificirani u tri
histološka gradusa; benigni, atipični i anaplastični. Većinom su benignog karaktera,
dok manji dio pripada višim gradusima s lošijom kliničkom slikom, povećanom stopom
recidiva i smrtnosti. Signalni put Notch je neophodan u embriogenezi, ali dokazana je
njegova uloga i u tumorigenezi. Protein NOTCH2 ovisno o vrsti tumora i tkiva može biti
onkogen ili tumor supresor, a njegova uloga u tumorigenezi meningeoma još nije
istražena. Cilj ovog diplomskog rada bio je istražiti metilaciju promotora gena i
ekspresiju proteina NOTCH2 u različitim gradusima intrakranijalnih meningeoma. U
ovom istraživanju, metilacija promotora gena NOTCH2 bila je značajno povezana s
atipičnim oblikom meningeoma. Metilacijski status gena NOTCH2 nije utjecao na
razinu ekspresije proteina. Analiza ekspresije proteina NOTCH2 pokazala je umjerenu
do jaku ekspresiju na razini citoplazme i stanične membrane u većini uzoraka
meningeoma te u kori velikog mozga zdrave osobe. Međutim, ekspresija na razini
jezgre je detektirana samo u tumorskom tkivu te je pozitivno korelirala s intenzitetom
ekspresije u citoplazmi. Rezultati ovog istraživanja upućuju na aktivnost signalnog puta
Notch i uključenost proteina NOTCH2 u tumorigenezi meningeoma.

Abstract (english)

Meningiomas are the most common primary tumors of the central nervous system
classified into three different histological grades; benign, atypical, and anaplastic. They
are usually benign, while smaller part belongs to higher grades with worse clinical
outcomes, higher recurrence, and mortality rates. The Notch signaling pathway is
crucial for embryogenesis and its part in carcinogenesis has also been proven.
Depending on tissue and tumor type, protein NOTCH2 can act as an oncogene or
tumor suppressor, but its role in meningioma tumorigenesis still remains unknown. The
aim of this master thesis was to examine gene promoter methylation and NOTCH2
protein expression in different grades of intracranial meningioma. In this study, gene
promoter methylation was significantly correlated with atypical meningioma and didn't
affect protein expression. Immunohistochemical analysis showed moderate to strong
cytoplasmatic and cell membrane protein expression in all meningioma samples,
including the cerebral cortex of a healthy person. However, expression in the nucleus
was only detected in tumor tissue and it positively correlated with the intensity of
cytoplasmatic expression. The results of this study indicate the activity of the Notch
signalling pathway and involvement of NOTCH2 in meningioma tumorigenesis.

• Keywords: intrakranijalni meningeomi; signalni put Notch; metilacijski obrazac promotora gena NOTCH2; ekspresija proteina NOTCH2
• Keywords (english): intracranial meningioma; Notch signaling pathway; NOTCH2 gene promoter methylation pattern; NOTCH2 protein expression
• Language: croatian
• URN:NBN: urn:nbn:hr:217:925913
• 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: Embargoed access; Embargo expiration date: 2025-02-23
• Created on: 2023-03-08 10:21:53