Strukturne promjene određenih gena u humanim tumorima zametnih stanica testisa

doctoral thesis

• Title (english): Structural alterations of selected genes in human testicular germ cell tumours
• Author: Tomislav Vladušić
• Mentor: Reno Hrašćan (mentor); MBZ: 187761
• Committee member: Jasna Franekić (član povjerenstva); MBZ: 85870
• Committee member: Nives Pećina-Šlaus (član povjerenstva)
• Committee member: Gordana Lacković-Venturin (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2013, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology
• Universal decimal classification (UDC): 575 - General genetics. General cytogenetics

Abstract

Tumori zametnih stanica testisa najčešće su maligne tvorbe u mladih muškaraca. Dvije histološke grupe, seminomi i neseminomi, razlikuju se morfološki i malignošću. Iako se uočava zajednička citogenetička promjena, amplifikacija 12p kromosomske regije, mehanizmi nastanka slabije agresivnih seminoma i izrazitije agresivnih neseminoma nisu poznati. Njihove molekularno-biološke studije često daju proturječne rezultate. Istražena je pojava strukturnih genskih promjena u 18 seminoma i 22 neseminoma u genima uključenim u maligni fenotip tumora: CDH1, APC (stanična diferencijacija i adhezija); NME1 (stanična pokretljivost); TP53, CDKN2A, RB1 (kontrola staničnog ciklusa i integriteta genoma); RAD51, MSH2, MLH1, BRCA1 (popravak oštecene DNA); BAX (apoptoza); ABCG2 (otpornost na ksenobiotike). Genske promjene, gubitak heterozigotnosti (LOH) i mikrosatelitna nestabilnost (MSI), istražene su koristeći polimorfizme u duljini restrikcijskih fragmenata ili duljini mikrosatelitnih ponavljanja. Uočena je razlika u strukturnim genskim promjenama seminoma i neseminoma. Profil genskih promjena ukazuje na njihovo zasebno podrijetlo, te jasno korelira s kliničkim ponašanjem tih tumora.

Abstract (english)

Testicular germ cell tumors are the most common malignacies in young males. Two histological groups, seminoma and nonseminoma, differ morphologically and in malignant behaviour. Although a common cytogenetic feature is seen, amplification of 12p chromosomal region, development mechanisms of weakly aggressive seminoma and more aggressive nonseminoma are unknown. Molecular biology studies of these tumors are often contradictory. Occurence of structural genetic alterations was analysed in 18 seminoma and 22 nonseminoma for genes involved in a malignant tumour phenotype: CDH1, APC (cellular differentiation and adhesion); NME1 (cellular motility); TP53, CDKN2A, RB1 (cell cycle and genome integrity control); RAD51, MSH2, MLH1, BRCA1 (DNA damage repair); BAX (apoptosis); ABCG2 (resistance to xenobiotics). Genetic alterations, loss of heterozygosity (LOH) and microsatellite instability (MSI), were analysed using restriction fragments length or microsatellite repeats length polymorphisms. A difference betwen structural genetic alterations in seminoma and nonseminoma has been observed. Occurence of genetic alterations indicate an independent development of seminoma and nonseminoma, and clearly correlates with clinical behaviour of those tumours.

• Keywords: tumori zametnih stanica testisa; seminom; neseminom; gubitak heterozigotnosti
• Keywords (english): testicular germ cell tumors; seminoma; nonseminoma; loss of heterozygosity
• Language: croatian
• URN:NBN: urn:nbn:hr:217:642069
• Study programme: Title: Biology; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje prirodnih znanosti, polje biologija (doktor/doktorica znanosti, područje prirodnih znanosti, polje biologija)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Access restricted to students and staff of home institution
• Created on: 2017-05-19 12:32:50