20.500.12556/RUL-127826 Opredelitev genetskih sprememb v genih CDKN2A in CDKN2B pri otrocih z B-celično akutno limfoblastno levkemijo Identification of genetic alterations in CDKN2A and CDNK2B genes in children with B cell acute lymphoblastic leukemia Akutna limfoblastna levkemija (ALL), ki je posledica rakavo spremenjene limfatične celice B ali T, je najpogostejša rakava bolezen pri otrocih. Uporaba visoko standardiziranih protokolov zdravljenja omogoča visoke stopnje preživetja, kljub temu pa je pri posameznikih z določenimi podtipi še vedno napoved slaba. Zato je izrednega pomena prepoznavanje dodatnih molekularno-genetskih dejavnikov, ki vplivajo na uspešno zdravljenje oz. ponovitev bolezni. V okviru magistrske naloge smo pri otrocih z B-celično ALL v tumor supresorskih genih CDKN2A in CDKN2B določali spremembe števila kopij genov z metodo MLPA (od ligacije odvisno hkratno pomnoževanje sond) in nukleotidne spremembe z metodo sekvenciranja po Sangerju. Pri več kot tretjini otrok v naši kohorti (43,3 %) so bile prisotne spremembe v genih CDKN2A oz. CDKN2B. Pogosteje je bilo prisotno spremenjeno število kopij gena kot pa sprememba nukleotidnega zaporedja. V preiskovani skupini so bile le pri 7,7 % otrok, ki so doživeli relaps ali smrt, prisotne spremembe enega nukleotida gena CDKN2A/2B. Največja pojavnost sprememb je bila v drugem eksonu gena CDKN2A. Na tem eksonu smo opredelili spremembo p.Ala148Thr (rs3731249) pri petih od 67 bolnikov. Glede na rezultate sklepamo, da nukleotidne spremembe na genu CDKN2A/2B niso odločilne za slabo prognozo oz. neodzivnost na klasično zdravljenje, zato uvedba te genetske analize v začetno diagnostiko ni smiselna. Acute lymphoblastic leukemia (ALL), characterized by malignant transformation of lymphoid cells B or T, is the most common cancer among children. While highly standardized treatment protocols enable high survival rates, some subtypes are still associated with poor prognosis. Therefore, identification of additional (molecular-genetic) factors affecting treatment failure or disease recurrence is of paramount importance. In this study, we analyzed copy number variation by MLPA (Multiplex Ligation-dependent Probe Amplification) method and DNA single nucleotide alterations with Sanger sequencing method present on tumor suppressor genes CDKN2A and CDKN2B in children with B-cell ALL. In our cohort more than one third of the patients had CDKN2A or CDKN2B alterations (43.3 %), where copy number variations were more common than single nucleotide variants. In the cohort only 7.7 % of children who experienced disease recurrence or death had CDKN2A/2B single nucleotide alterations. Variants were most frequently present in the second exon of the CDKN2A gene. In this exon we identified a variant p.Ala148Thr (rs3731249) which was present in five out of 67 patients. In this cohort, CDKN2A/2B single nucleotide variants were not an important factor influencing poor prognosis or resistance to classical treatment, therefore implementation of this genetic analysis into diagnostic procedure is not reasonable. B-celična akutna limfoblastna levkemija delecije genov CDKN2A in CDKN2B nukleotidne spremembe CDKN2A/2B prognoza B-cell acute lymphoblastic leukemia CDKN2A and CDKN2B genes deletions CDKN2A/2B single nucleotide alterations prognosis true false false Slovenski jezik Angleški jezik Magistrsko delo/naloga 2021-06-24 08:45:02 2021-06-24 08:45:08 2022-09-06 03:53:19 0000-00-00 00:00:00 2021 0 0 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 1970-01-01 81082 1846.pdf 1846.pdf 1 A5B75DF8179A36897099135FF0E2B38D 52bedeef584658999bcfb5c46c6022dd7d4d7eb88820f6f6f3dafae9eaa05e63 9a4aba21-d4b7-11eb-a523-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=144379 Fakulteta za farmacijo 0 0 0