Polimorfizmi gena BIRC5 i ekspresija izoformi proteina survivina u karcinomu dojke

master's thesis

• Title (english): BIRC5 gene polymorphisms and expression of survivin protein isoforms in breast cancer
• Author: Magdalena Vincetić
• Mentor: Vesna Musani (mentor)
• Mentor: Inga Marijanović (sumentor)
• Committee member: Inga Marijanović (predsjednik povjerenstva)
• Committee member: Silvija Černi (član povjerenstva)
• Committee member: Jasna Lajtner (član povjerenstva)
• Committee member: Sandra Radić Brkanac (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2020-02-28, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Karcinom dojke je jedan od najčešćih karcinoma i vodeći je uzrok smrti od raka kod žena diljem svijeta i u Hrvatskoj. Postoje jako velike razlike u preživljenju kod pacijentica zbog čega postoji potreba za otkrivanje osjetljivih dijagnostičkih i prognostičkih markera. Survivin, kodiran genom BIRC5, je jedan od proteina inhibitora stanične smrti i njegova razina je znatno povećana u gotovo svim tumorima dok u normalnim diferenciranim tkivima odraslih organizama nije eksprimiran. U karcinomu dojke je njegova ekspresija povezana s povećanom otpornošću na kemo- i radioterapiju, višim histološkim stupnjem, mlađom dobi obolijevanja, veličinom tumora i negativnim statusom estrogenskih receptora. Istraživala sam polimorfizme gena BIRC5 i ekspresiju različitih izoformi survivina u karcinomu dojke metodom analize heterodupleksa, sekvenciranjem DNA i metodom qRT-PCR. Pronašla sam jedanaest polimorfizama gena BIRC5 i njihove frekvencije u pacijenticama s karcinomom dojke se nisu značajno razlikovale od frekvencija u zdravim kontrolama. Čini se da polimorfizmi gena BIRC5 nemaju značajnu ulogu u nastanku karcinoma dojke, no moguće je da bi veći broj uzoraka pokazao drugačije rezultate. Pretpostavka da se određivanjem razine ekspresije nekih izoformi gena BIRC5 može razlikovati tumorsko od zdravog tkiva potvrđena je za pet od osam izoformi.

Abstract (english)

Breast cancer is one of the most common cancers and is the leading cause of cancer deaths in women worldwide and in Croatia. There are very large differences in patient survival, which is why there is a need to detect sensitive diagnostic and prognostic markers. Survivin, encoded by the BIRC5 gene, is one of the proteins of cell death inhibitors (apoptosis) and its level is significantly increased in almost all tumors, whereas it is not expressed in normal differentiated tissues of adult organisms. In breast cancer, its expression is associated with increased resistance to chemo- and radiotherapy, higher histologic grade, younger age, tumor size and negative estrogen receptor status. I studied BIRC5 gene polymorphisms and expression of various survivin isoforms in breast cancer by heteroduplex analysis, DNA sequencing, and qRT-PCR. I found eleven BIRC5 gene polymorphisms and their frequencies in patients with breast cancer did not differ significantly from the frequencies in healthy controls. BIRC5 gene polymorphisms do not appear to play a significant role in the development of breast cancer, but it is possible that a larger sample size would show different results. The assumption that by determining the expression level of some isoforms of the BIRC5 gene can be differentiated tumor-free from healthy tissue was confirmed for five of the eight isoforms.

• Keywords: survivin; gen BIRC5; polimorfizmi; izoforme; karcinom dojke
• Keywords (english): survivin; BIRC5 gene; polymorphisms; isoforms; breast cancer
• Language: croatian
• URN:NBN: urn:nbn:hr:217:093083
• 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: 2022-02-28
• Created on: 2020-07-13 08:52:22