. "\u010Cern\u00E1, K." . "Modern\u00ED dagnostika Lynchova syndromu" . "Stehl\u00EDk, L." . "RIV/00216208:11140/14:10283829!RIV15-MSM-11140___" . "8"^^ . . "Gastroenterologie a hepatologie" . . "30060" . . "Du\u0161ek, Martin" . "2" . . "Hadravsk\u00FD, Ladislav" . "Lynch\u016Fv syndrom (d\u0159\u00EDve zvan\u00FD heredit\u00E1rn\u00ED nepolyp\u00F3zn\u00ED kolorekt\u00E1ln\u00ED karcinom) je nej\u010Dast\u011Bj\u0161\u00ED genetickou p\u0159\u00ED\u010Dinou famili\u00E1rn\u00EDho v\u00FDskytu kolorekt\u00E1ln\u00EDho karcinomu. P\u0159\u00ED\u010Dinou je z\u00E1rode\u010Dn\u00E1 mutace n\u011Bkter\u00E9ho z MMR gen\u016F, kter\u00E9 jsou zodpov\u011Bdn\u00E9 za opravy chyb ve struktu\u0159e DNA vznikaj\u00EDc\u00ED p\u0159i jej\u00ED replikaci. Tyto mutace zp\u016Fsobuj\u00ED dysfunkci opravn\u00E9ho komplexu, kter\u00E1 vede k rozvoji nestability mikrosatelit\u016F (MSI) a ke vzniku a progresi n\u00E1dor\u016F, zejm\u00E9na kolorekt\u00E1ln\u00EDho karcinomu. V sou\u010Dasn\u00E9 dob\u011B se odhaduje, \u017Ee a\u017E 5 % kolorekt\u00E1ln\u00EDch karcinom\u016F vznik\u00E1 v asociaci s Lynchov\u00FDm syndromem. Vzhledem k t\u00E9to pom\u011Brn\u011B vysok\u00E9 \u010Detnosti, absenci premorbidn\u00EDho fenotypu, famili\u00E1rn\u00EDmu v\u00FDskytu a prezentaci malign\u00EDch n\u00E1dor\u016F v produktivn\u00EDm v\u011Bku je v\u010Dasn\u00E1 diagnostika Lynchova syndromu d\u016Fle\u017Eit\u00E1 nejen z etick\u00E9ho, ale i ekonomick\u00E9ho hlediska. Bohu\u017Eel, Bethesda guidelines, nato\u017E Amsterdamsk\u00E1 krit\u00E9ria, nejsou dostate\u010Dn\u011B senzitivn\u00ED. Vy\u0161\u0161\u00ED senzitivitu vykazuje detekce morfologick\u00FDch znak\u016F asociovan\u00FDch s MSI p\u0159i histologick\u00E9m vy\u0161et\u0159en\u00ED vzork\u016F kolorekt\u00E1ln\u00EDch karcinom\u016F. P\u0159ibli\u017En\u011B jedna p\u011Btina karcinom\u016F s MSI je geneticky podm\u00EDn\u011Bna Lynchov\u00FDm syndromem, zbytek tvo\u0159\u00ED sporadick\u00E9 MSI-H karcinomy zp\u016Fsoben\u00E9 epigenetickou inaktivac\u00ED MMR genu. K vylou\u010Den\u00ED t\u011Bchto sporadick\u00FDch p\u0159\u00EDpad\u016F z dal\u0161\u00EDho testov\u00E1n\u00ED slou\u017E\u00ED vy\u0161et\u0159en\u00ED genu BRAF a anal\u00FDza metylace promotoru genu MLH1. Podez\u0159en\u00ED na Lynch\u016Fv syndrom vypl\u00FDvaj\u00EDc\u00ED z v\u00FDsledk\u016F v\u00FD\u0161e uveden\u00E9ho komplexu vy\u0161et\u0159en\u00ED by m\u011Blo b\u00FDt nakonec potvrzeno detekc\u00ED z\u00E1rode\u010Dn\u00E9 mutace n\u011Bkter\u00E9ho z MMR gen\u016F v perifern\u00ED krvi pacienta s n\u00E1sledn\u00FDm vy\u0161et\u0159en\u00EDm rodinn\u00FDch p\u0159\u00EDslu\u0161n\u00EDk\u016F pro zaji\u0161t\u011Bn\u00ED \u00FA\u010Dinn\u00E9 prevence."@cs . "RIV/00216208:11140/14:10283829" . . . . "Lynch syndrome (formerly known as hereditary non-polyposis colorectal cancer) is the most common hereditary colorectal cancer syndrome. The syndrome is caused by a germline mutation of one of the mismatch repair (MMR) genes which are responsible for DNA replication error repair. Impaired function of the proteins encoded by these genes leads to microsatellite instability (MSI) and forms a suitable background for development and progression of tumours, mainly colorectal cancer. According to recent estimates up to 5% of all cases of colorectal cancer are associated with Lynch syndrome. Due to this relatively high frequency, familial occurrence, absence of premorbid phenotype and development of malignant tumors in productive age, correct diagnosis is important not only from the ethical but also the economical point of view. Unfortunately, clinical means of diagnostics of Lynch syndrome (like the Amsterdam criteria and Bethesda guidelines) lacks sensitivity. It was shown that predictive models based on histological signs of MSI are more sensitive than the clinical criteria used to detect patients with suspected Lynch syndrome. Of all MSI-H colorectal cancers, 1/5 is caused by Lynch syndrome, while the rest are sporadic cancers caused by epigenetic inactivation of an MMR gene. To rule out the sporadic cases, molecular genetic investigation of the BRAF gene and methylation analysis of the MLH1 promoter is used in the diagnostic workup of Lynch syndrome. The suspicion of Lynch syndrome, based on the results of the complex of diagnostic methods mentioned above, should be proved by detection of a germline mutation of an MMR gene in peripheral blood, and followed by screening of family members, which is a necessary condition for efficient prevention."@en . . "11140" . "Bene\u0161, Z." . . "Modern diagnostics of Lynch syndrome"@en . "[8BD355F9BA2F]" . . "Michal, Michal" . "Koko\u0161kov\u00E1, Bohuslava" . "Modern diagnostics of Lynch syndrome"@en . "Modern\u00ED dagnostika Lynchova syndromu" . . . "CZ - \u010Cesk\u00E1 republika" . "Modern\u00ED dagnostika Lynchova syndromu"@cs . "68" . "I" . "9"^^ . "Modern\u00ED dagnostika Lynchova syndromu"@cs . . "Lynch\u016Fv syndrom (d\u0159\u00EDve zvan\u00FD heredit\u00E1rn\u00ED nepolyp\u00F3zn\u00ED kolorekt\u00E1ln\u00ED karcinom) je nej\u010Dast\u011Bj\u0161\u00ED genetickou p\u0159\u00ED\u010Dinou famili\u00E1rn\u00EDho v\u00FDskytu kolorekt\u00E1ln\u00EDho karcinomu. P\u0159\u00ED\u010Dinou je z\u00E1rode\u010Dn\u00E1 mutace n\u011Bkter\u00E9ho z MMR gen\u016F, kter\u00E9 jsou zodpov\u011Bdn\u00E9 za opravy chyb ve struktu\u0159e DNA vznikaj\u00EDc\u00ED p\u0159i jej\u00ED replikaci. Tyto mutace zp\u016Fsobuj\u00ED dysfunkci opravn\u00E9ho komplexu, kter\u00E1 vede k rozvoji nestability mikrosatelit\u016F (MSI) a ke vzniku a progresi n\u00E1dor\u016F, zejm\u00E9na kolorekt\u00E1ln\u00EDho karcinomu. V sou\u010Dasn\u00E9 dob\u011B se odhaduje, \u017Ee a\u017E 5 % kolorekt\u00E1ln\u00EDch karcinom\u016F vznik\u00E1 v asociaci s Lynchov\u00FDm syndromem. Vzhledem k t\u00E9to pom\u011Brn\u011B vysok\u00E9 \u010Detnosti, absenci premorbidn\u00EDho fenotypu, famili\u00E1rn\u00EDmu v\u00FDskytu a prezentaci malign\u00EDch n\u00E1dor\u016F v produktivn\u00EDm v\u011Bku je v\u010Dasn\u00E1 diagnostika Lynchova syndromu d\u016Fle\u017Eit\u00E1 nejen z etick\u00E9ho, ale i ekonomick\u00E9ho hlediska. Bohu\u017Eel, Bethesda guidelines, nato\u017E Amsterdamsk\u00E1 krit\u00E9ria, nejsou dostate\u010Dn\u011B senzitivn\u00ED. Vy\u0161\u0161\u00ED senzitivitu vykazuje detekce morfologick\u00FDch znak\u016F asociovan\u00FDch s MSI p\u0159i histologick\u00E9m vy\u0161et\u0159en\u00ED vzork\u016F kolorekt\u00E1ln\u00EDch karcinom\u016F. P\u0159ibli\u017En\u011B jedna p\u011Btina karcinom\u016F s MSI je geneticky podm\u00EDn\u011Bna Lynchov\u00FDm syndromem, zbytek tvo\u0159\u00ED sporadick\u00E9 MSI-H karcinomy zp\u016Fsoben\u00E9 epigenetickou inaktivac\u00ED MMR genu. K vylou\u010Den\u00ED t\u011Bchto sporadick\u00FDch p\u0159\u00EDpad\u016F z dal\u0161\u00EDho testov\u00E1n\u00ED slou\u017E\u00ED vy\u0161et\u0159en\u00ED genu BRAF a anal\u00FDza metylace promotoru genu MLH1. Podez\u0159en\u00ED na Lynch\u016Fv syndrom vypl\u00FDvaj\u00EDc\u00ED z v\u00FDsledk\u016F v\u00FD\u0161e uveden\u00E9ho komplexu vy\u0161et\u0159en\u00ED by m\u011Blo b\u00FDt nakonec potvrzeno detekc\u00ED z\u00E1rode\u010Dn\u00E9 mutace n\u011Bkter\u00E9ho z MMR gen\u016F v perifern\u00ED krvi pacienta s n\u00E1sledn\u00FDm vy\u0161et\u0159en\u00EDm rodinn\u00FDch p\u0159\u00EDslu\u0161n\u00EDk\u016F pro zaji\u0161t\u011Bn\u00ED \u00FA\u010Dinn\u00E9 prevence." . . . . . "microsatellite instability; MSI; HNPCC; Lynch syndrome; colorectal cancer"@en . "Daum, Ond\u0159ej" . . "5"^^ . "1804-7874" . .