Nestabilnost mikrosatelitne DNA i analiza gena hMSH2 u sporadičnim karcinomima debelog crijeva

master's thesis

• Title (english): Microsatellite instability and hMSH2 gene analysis in sporadic colon cancer
• Author: Patricia Jukić
• Mentor: Tamara Čačev (mentor)
• Mentor: Maja Matulić (mentor)
• Committee member: Maja Matulić (predsjednik povjerenstva)
• Committee member: Tamara Čačev (član povjerenstva)
• Committee member: Mirjana Kalafatić (član povjerenstva)
• Committee member: Inga Marijanović (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2013-07-08, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Oko 15% sporadičnih karcinoma debelog crijeva nastaje mutatorskim putem karcinogeneze kojeg karakterizira nestabilnost mikrosatelitne DNA (MSI) uzrokovana promjenama u genima iz sustava popravka krivo sparenih baza (MMR). Ovi tumori imaju različite molekularne i kliničko-patološke karakteristike, te odgovor na terapiju u odnosu na tumore s intaktnim sustavom MMR. U ovom radu analiziran je gubitak heterozigotnosti (LOH) gena hMSH2, ključnog gena sustava MMR, te učestalost nestabilnosti mikrosatelitne DNA na uzorku od 100 oboljelih od sporadičnog karcinoma debelog crijeva te su rezultati korelirani s kliničko-patološkim karakteristikama. U ispitivanju statusa LOH i MSI korištena je analiza biljega VNTR D2S123 i D2S378 odnosno fragmentarna analiza 5 biljega panela Bethesda. Informativnim se pokazalo 85 uzoraka, LOH je bio prisutan u 9.4%, a visoka MSI u 8.2% analiziranih tumora. Nije bilo statistički značajne korelacije između učestalosti LOH/MSI i kliničko-patoloških značajki oboljelih, iako je LOH/MSI bio češći u većim, slabije diferenciranim i uznapredovalim tumorima.

Abstract (english)

Approximately 15% of sporadic colorectal carcinomas (CRC) arise from mutator carcinogenic pathway which is characterized by microsatellite instability (MSI) caused by deficient mismatch repair system (MMR), secondary to defects in one of MMR genes. These tumors have distinct molecular and clinical-pathological features and different response to therapy. In this study we have examined the loss of heterozygosity (LOH) at the hMSH2 gene, a crucial gene in MMR system, by VNTR (D2S123 and D2S378) analysis and microsatellite instability (MSI) using the Bethesda panel of 5 microsatellite markers in 100 CRC patients. Results were compaired with clinico-pathological characteristics of patients and their tumors. LOH was detected in 9.4% and high MSI in 8.2% analysed tumors. There was no statictically significant correlation between the LOH/MSI and clinico-pathological characteristics, although LOH/MSI was more frequent in larger, poorly differentiated and advanced stage tumors.

• Keywords: hMSH2; sporadični rak debelog crijeva; LOH i MSI
• Keywords (english): hMSH2; sporadic colorectal cancer; LOH; MSI
• Language: croatian
• URN:NBN: urn:nbn:hr:217:272049
• 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: Access restricted to students and staff of home institution
• Created on: 2017-04-27 08:48:03