Genetika Lynch sindroma

master's thesis

• Title (english): Genetic basis of Lynch syndrome
• Author: Ivana Lukša
• Mentor: Tamara Nikuševa Martić (mentor)
• Committee member: Frane Paić (predsjednik povjerenstva)
• Committee member: Ljiljana Šerman (član povjerenstva)
• Committee member: Tamara Nikuševa Martić (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Medical Biology); Zagreb
• Defense date and country: 2019-07-12, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Medical Microbiology
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Human Genetics, Genomics and Proteomics

Abstract

Lynch sindrom najčešći je oblik nasljednog nepolipoznog karcinoma kolona. Karakteriziran je povećanim rizikom za pojavljivanje karcinoma kolona, endometrija, jajnika i želuca te po nešto manjem riziku pojavljivanja nekih karcinoma izvan kolona. Može se podijeliti na tip 1 i tip 2 ovisno o tome postoje li karcinomi izvan kolona ili ne. Visoki rizik za razvoj karcinoma posljedica je mutacija u genima za mismatch repair. Nemogućnost popravka DNA uzrokuje nakupljanje točkastih mutacija što nadalje uzrokuje mikrosatelitnu nestabilnost. Lynch sindrom nasljeđuje se autosomno dominantno što znači da je dovoljan jedan mutirani alel da se rizik poveća, a može se naslijediti od oba roditelja. Rizik za nasljeđivanje mutiranog alela u potomka oboljelog roditelja iznosi 50%. Poznavanje genetike Lynch sindroma omogućuje probir, praćenje i pravovremeno dijagnosticiranje i liječenje pacijenata. Kako Lynch sindrom spada u grupu nasljednih nepolipoznih kolorektalnih karcinoma, za dijagnozu se koriste Amsterdamski kriteriji I, II i Bethesda revidirani kriteriji. Oni pokazuju u kojem slučaju je korisno testirati tumorsko tkivo na mutacije povezane uz Lynch sindrom i kada genetski testirati pacijenta ili članove njegove obitelji uzimajući uzorak krvi. Iako se u liječenju danas koriste protokoli kemoterapije koji nisu uvijek uspješni, postoji nada za pacijente s Lynch sindromom. Razvijena su monoklonska protutijela koja su uspješna u ciljnom uništavanju tumora uzrokovanima mikrosatelitnom nestabilnošću. Iz toga proizlazi da je zaista važno poznavati genetsku podlogu sindroma koje liječimo.

Abstract (english)

Lynch sindrome is the most common form of hereditary nonpolyposis colorectal cancer. In its core is elevated risk for developing colon, endometrial, ovarian and stomach carcinoma while risk for developing other types of carcinomas is lower, but still exists. There are two types of Lynch sindrom classified considering the presence of extracolonic carcinomas. High risk for developing tumors is a direct consequence of mutations in mismatch repair genes. Cell's ability to repair DNA has been compromised which results in accumulation of point mutations and microsatellite instability. Inheritance of Lynch syndrome is autosomal dominant which means one mutated allele is enough to cause elevation of risk for developing carcinoma and it can be inherited by both parents. Risk for inheritence of mutated allele in an offspring is 50%. Being familiar with Lynch sindrome genetics makes it possible for patients to be screened, checked up regularly, diagnosed early and treated properly. Since Lynch syndrome is a form of hereditary nonpolyposis colorectal cancer, Amsterdam criteria I, II and revised Bethesda guidlines can be used in diagnosis. These criteria and guidelines help to determine when is necessary to test tumor tissue for mutations and when to perform genetic tests on patients and their family members using their blood samples. Although protocols of chemotherapy used in treatment are not always succesfull, there is hope for patients with Lynch syndrome. In development are monoclonal antibodies that are succesful in targeting tumors caused by microsatellite instability. That shows how important it is to know about genetic basis of syndromes we treat.

• Keywords: rizik; karcinom kolona; mismatch repair; mikrosatelitna nestabilnost
• Keywords (english): risk; colon carcinoma; mismatch repair; microsatellite instability
• Language: croatian
• URN:NBN: urn:nbn:hr:105:178447
• Study programme: Title: Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2019-12-19 09:05:48