Vpliv genetske variabilnosti v izbranih proteinskih kinazah celičnega cikla na razvoj raka želodca.

Babič, Denis (author), Hudler, Petra (mentor)

Rak želodca je 8. najpogostejši rak v Sloveniji, njegova pojavnost pa se v zadnjih letih ustaljuje. Je bolezen starejših, saj je povprečna starost pacientov več kot 60 let. Rak je heterogena populacija celic, ki so izgubile nadzor nad delitvijo. Nastanek raka je posledica prepleta okoljskih in genetskih dejavnikov, kot so na primer genetske spremembe v DNA ali spremembe v izražanju mRNA. Nekateri polimorfizmi lahko povzročijo kromosomsko nestabilnost. To privede do okvar različnih mehanizmov, zaradi česar se celice začno nenadzorovano deliti. Z bioinformacijskimi orodji smo izbrali kandidatni gen NEK6, ki nosi zapis za segregacijsko kinazo. Ta uravnava in skrbi za pravilno vzpostavitev delitvenega vretena med celično delitvijo. Z informacijskimi orodji smo nato izbrali polimorfizem rs2416, ki leži v 3'-neprevedeni regiji, in rs2065221 v intronski regiji. Namen magistrske naloge je bil izbrati kandidatne genetske variacije ter določiti njihov vpliv na nastanek raka želodca. Analizirali smo vzorce DNA iz tkiv pacientov s tovrstnim rakom in vzorce DNA iz krvi zdravih posameznikov. S statističnimi metodami smo nato opredelili in določili povezavo med genotipi kandidatnih polimorfizmov in nastankom raka na želodcu.

• Language: Slovenian
• Keywords: Rak želodca, dejavniki tveganja, genetski dejavniki, kromosomska nestabilnost, polimorfizem enojnega nukleotida, proteinska kinaza, NEK6
• Work type: Master's thesis/paper
• Typology: 2.09 - Master's Thesis
• Organization: BF - Biotechnical Faculty
• Place of publishing: Ljubljana
• Publisher: [D. Babič]
• Year: 2021
• PID: 20.500.12556/RUL-129115
• UDC: 606:616-006.6:601.4:577.21:591.151(043.2)
• COBISS.SI-ID: 74527491
• Publication date in RUL: 27.08.2021

Secondary language

• Language: English
• Title: Association of genetic variability in segregation kinases with gastric cancer susceptibility

Abstract

Gastric cancer is the 8th most common cancer in Slovenia, and its incidence has been stabilizing in recent years. It is the disease of the elderly, as the average age of patients is over 60 years. Cancer is a heterogeneous population of cells that have lost control of controlled division. Tumour is caused by a combination of environmental and genetic factors, including genetic variations in the DNA sequence and alterations of mRNAs expression. Specific single nucleotide polymorphisms can cause chromosomal instability. This leads to impairment of various mechanisms, causing the cells to start dividing uncontrollably. Using bioinformatics tools, we selected the candidate gene NEK6, which encodes a segregation kinase. This enzyme regulates and ensures proper establishment of the mitotic spindle during cell division. Using informatics tools, we selected the polymorphism rs2416, which lies on the 3'-UTR region, and rs2065221, which is located in the intron region. The purpose of this master's thesis was to select candidate genetic variations and determine their impact on the development of gastric cancer. The analysis was performed on DNA samples from tissues of patients with gastric cancer and on DNA samples from the blood of healthy individuals. Selected statistical methods were used to define and determine the association of candidate polymorphisms with the development of gastric cancer.

• Keywords: Gastric cancer, risk factors, genetic risks, chromosomal instability, single nucleotide polimorfism, segregation kinase, NEK6