"http://www.isvav.cz/projectDetail.do?rowId=NT14054"^^ . . "NT14054" . . . "1"^^ . "2014-03-21+01:00"^^ . "0"^^ . . "0"^^ . . "0"^^ . " cancer predisposition" . " DNA damage response genes" . . . . "hereditary breast cancer; cancer predisposition; DNA damage response genes; high-throughput sequencing; functional analysis; genotyping"@en . "0"^^ . . "Candidate genetic BC predisposition factors will be identified using the next-gen sequencing on SOLiD4 analyzer. Entire coding sequence of >250 selected genes isolated by exon trapping will be analyzed in 300 samples of high-risk (BRCA1/2-negative) BC patients and 300 controls. Following the mapping of sequencing data and bioinformatics analysis, the variants differing in frequency between analyzed sample sets will be validated in the independent sample sets of high risk patients (+250), unselected BC patients (600) and controls (600). Simultaneously, the functional effect of selected variants in mammary tumorigenesis will be studied in BC cell lines. The cells expressing transfected variants will be analyzed considering the cell viability upon genotoxic stress and DNA-repair kinetics. Influence of candidate alterations on prediction/prognosis of BC in their carriers/non-carriers will be statistically evaluated."@en . "hereditary breast cancer" . . . "C\u00EDlen\u00E9 NEXT-GEN sekvenov\u00E1n\u00ED jako p\u0159\u00EDstup k identifikaci predispozi\u010Dn\u00EDch gen\u016F pro vznik karcinomu prsu u vysoce rizikov\u00FDch pacient\u016F" . "2013-05-01+02:00"^^ . "Kandid\u00E1tn\u00ED genetick\u00E9 predispozi\u010Dn\u00ED faktory ovliv\u0148uj\u00EDc\u00ED riziko vzniku ca prsu budou identifikov\u00E1ny pomoc\u00ED next-gen sekvenov\u00E1n\u00ED na analyz\u00E1toru SOLiD4. K\u00F3duj\u00EDc\u00ED sekvence >250 gen\u016F izolovan\u00E1 selektivn\u00ED hybridizac\u00ED (exon trapping) bude analyzov\u00E1na u 300 vzork\u016F rizikov\u00FDch BRCA1/2-negativn\u00EDch pacient\u016F s ca prsu a 300 kontrol. Po mapov\u00E1n\u00ED a bioinformatick\u00E9 anal\u00FDze bude validace alterac\u00ED se statisticky odli\u0161nou frekvenc\u00ED v\u00FDskytu mezi studovan\u00FDmi soubory provedena genotypiza\u010Dn\u00EDmi postupy (DHPLC a HRM) v roz\u0161\u00ED\u0159en\u00FDch souborech vzork\u016F vysoce rizikov\u00FDch pacientek (+250), neselektovan\u00E9ho ca prsu (600) a kontrol (600). Funk\u010Dn\u00ED vliv vybran\u00FDch alterac\u00ED v mam\u00E1rn\u00ED tumorogenezi bude simult\u00E1nn\u011B studov\u00E1n in vitro v modelech lini\u00ED ca prsu. Zkonstruovan\u00E9 klony bun\u011Bk exprimuj\u00EDc\u00ED studovan\u00E9 varianty budou analyzov\u00E1ny s ohledem na viabilitu bun\u011Bk po genotoxick\u00E9m po\u0161kozen\u00ED a kinetiku DNA reparace. Vliv kandid\u00E1tn\u00EDch alterac\u00ED na predikci/progn\u00F3zu ca prsu u jejich nosi\u010D\u016F bude statisticky vyhodnocen." . " high-throughput sequencing" . . . . "Targeted NEXT-GEN sequencing as a tool for identification of the new breast cancer susceptibility genes in high-risk patients"@en . "2015-12-31+01:00"^^ . . . . " functional analysis" . "2015-01-22+01:00"^^ . .