"5"^^ . . "Promoter methylation analysis of the genes downstream of BRCA1 and BRCA1 - comparison of methylation profiles in mutation carriers and non-carriers"@en . "This project was design to test the hypothesis that tissue of individuals with germline mutations in BRCA1 or BRCA2 genes show a specific methylation profile that distinguishes them from individuals without the mutation and affects cellular mechanisms in which the products of methylated genes are involved.The analysis revealed validity of this hypothesis on three levels: 1) differences of DNA met"@en . "1"^^ . "BRCA1; BRCA2; methylation; hereditary breast/ovarian cancer"@en . . . "2008-01-01+01:00"^^ . "0"^^ . . "0"^^ . "GP301/08/P103" . "Anal\u00FDza metylace promotor\u016F gen\u016F interaguj\u00EDc\u00EDch s proteiny BRCA1 a BRCA2 nebo jimi ovlivn\u011Bn\u00FDch - srovn\u00E1n\u00ED nosi\u010D\u016F mutac\u00ED a jedinc\u016F bez mutace" . . "2010-12-31+01:00"^^ . . . "http://www.isvav.cz/projectDetail.do?rowId=GP301/08/P103"^^ . . "U jedinc\u016F s\u00A0mutac\u00ED v\u00A0genech BRCA1/2 pozorujeme r\u016Fznou penetranci stejn\u00FDch mutac\u00ED. P\u0159edpokl\u00E1d\u00E1me existenci faktor\u016F, kter\u00E9 ovliv\u0148uj\u00ED m\u00EDru uplatn\u011Bn\u00ED d\u011Bdi\u010Dn\u00E9 dispozice (tzv. cancer risk modifiers). Nejedn\u00E1 se o vlivy zevn\u00ED, ale o genetick\u00E9 a epigenetick\u00E9 zm\u011Bny struktury DNA. \u010Casto je studov\u00E1na metylace promotorov\u00FDch sekvenc\u00ED r\u016Fzn\u00FDch gen\u016F. Tato zm\u011Bna m\u016F\u017Ee potla\u010Dit nebo pos\u00EDlit expresi genu. Informace z\u00A0t\u00E9to oblasti na poli v\u00FDzkumu d\u011Bdi\u010Dn\u00E9 dispozice ke vzniku karcinomu prsu a vaje\u010Dn\u00EDk\u016F jsou sice slibn\u00E9, ale jen \u00FAtr\u017Ekovit\u00E9. Odli\u0161nost expresn\u00EDho profilu nositel\u016F mutac\u00ED gen\u016F BRCA1/2 vedla k\u00A0vysloven\u00ED hypot\u00E9zy: Tk\u00E1n\u011B jedinc\u016F se z\u00E1rode\u010Dnou mutac\u00ED v\u00A0genech BRCA1 a BRCA2 vykazuj\u00ED specifick\u00FD metyla\u010Dn\u00ED profil, kter\u00FD je odli\u0161uje od jedinc\u016F bez mutace a ovliv\u0148uje bun\u011B\u010Dn\u00E9 mechanismy, jich\u017E se produkty metylovan\u00FDch gen\u016F \u00FA\u010Dastn\u00ED.Bylo prok\u00E1z\u00E1no, \u017Ee genetick\u00E9 pozad\u00ED jednotlivce m\u00E1 vliv na m\u00EDru metylace promotorov\u00FDch sekvenc\u00ED jednotliv\u00FDch gen\u016F. V\u00A0na\u0161em navrhovan\u00E9m projektu chceme analyzovat m\u00EDru metylace promotorov\u00FDch" . . . . . . "BRCA1" . . . " BRCA2" . "2015-03-20+01:00"^^ . " methylation" . "C\u00EDlem projektu bylo ov\u011B\u0159it hypot\u00E9zu, \u017Ee tk\u00E1n\u011B jedinc\u016F se z\u00E1rode\u010Dnou mutac\u00ED v genech BRCA1 a BRCA2 vykazuj\u00ED specifick\u00FD metyla\u010Dn\u00ED profil, kter\u00FD je odli\u0161uje od jedinc\u016F bez mutace a ovliv\u0148uje bun\u011B\u010Dn\u00E9 mechanismy, jich\u017E se produkty metylovan\u00FDch gen\u016F \u00FA\u010Dastn\u00ED. Proveden\u00E9 anal\u00FDzy prok\u00E1zaly pravdivost t\u00E9to hypot\u00E9zy na t\u0159ech \u00FArovn\u00EDch: 1) odli\u0161nost metyla\u010Dn\u00EDho profilu DNA perifern\u00ED krve mezi nosi\u010Dkami mu"@cs . . "2010-04-16+02:00"^^ . . . . . "Different penetrance of identical mutations is observed in BRCA1/2 genes mutation carriers. There is an extensive search for cancer risk modifier factors. These are not extrinsic factors, but genetic and epigenetic changes of DNA. Promoter methylation ofvarious genes is thought to be an important actor as it can influence gene\u00B4s expresion. Experiments considering methylation are extremely exciting but just sketchy at present time.The expression profile difference of BRCA1/2 mutation carriers allows to formulate hypothesis: There is a specific methylation profiles in BRCA1/2 mutation carriers discriminating them from non-carriers and influencing cell mechanisms, in which products of methylated genes are involved.There is certain evidence that genetic background influences promoter methylation. We propose to identify specific methylation profile of germ-line BRCA1/2 mutation carriers and learn how it impresses penetrance and disease characteristics."@en . "5"^^ .