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2
Maligní nádorová onemocnění 
MALIGNÍ PROCES – VÍCESTUPŇOVÝ
<= span style=3D'font-size:75%'>ně= kolik na sobě nezávislých změn v genomu jedné buňky
<= span style=3D'font-size:75%'>premali= gní stádium / maligní stádium
mutace v protoonkogenech, tumor-supresorov&yacu= te;ch genech, mut&= aacute;torových genech
EPIGENETICKÉ FAKTORY
<= span style=3D'font-size:75%'>genomic= ký imprinting - souvislost s metylací bazí genů <= /span>
        = ;            &n= bsp;            = ;            &n= bsp;            = ;    (př. Wilmsův tumor)
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3
3Dimage003 <= ![endif]>
FAP – VÍCESTUPŇOVÝ MALIGNÍ PROCES
<= ![if !vml]>
Mutace APC (5q21) – hyperplastický střevní epitel
Hypometylace DNA – časné adenomy
Mutace onkogenu K-ras (12p) = 211; střední adenomatozní stádium
DCC gen (18q) – pozdní stádium polypů =
Gen TP53 (17p) – karcinom <= /div>
Další změny – metastazování
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4
3D9711gen4=
Protoonkogeny
PROTOONKOGENY – geny se skrytým onkogenním potenciálem
•<= /span>REGULACE BUNĚČNÉHO MNOŽENÍ NA VŠECH ÚROVNÍCH SIGNÁLNÍCH DRAH
•<= /span>většinou somatické mutace – dominantní charakter <= /span>
MUTACE - typy=
bodové – substituce, delece, adice
chromosomální přestavby<= /i> – translokace, amplifikace
inserce virového genomu
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5
Protoonkogeny – úloha v regulaci buněčného dělen&iacu= te;
<= span style=3D'font-size:75%'>Rů= stové faktory: sis= - PDGF, hst – FGF
Receptory růstových faktorů: proteiny s ty= rosinkinázovou aktivitou - erb-B – receptor pro EGF
Proteiny vázající  GTP (G-proteiny): genová rodina ras
Tyrosinkinázy plasmatické membrány: fosforylace tyrosinu – abl, src
Cytoplasmatické proteiny: MAP-kiná= ;zy Raf, MEK, MAP (signál cytoplasma jádro)
Transkr= ipční faktory: protoonkogen fos, = jun, erb-A
Kontrola buněčného cyklu: protoonkogen myc, myb stimulují přechod z G1 do S fáze
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6
Protoonkogen c-ras - sign= ální dráha
P= 45;íklad str. 145 =
•<= /span>Definujte typ mutace v protoonkogenu c-ras.
•<= /span>Jak ovlivní tato mutace přenos signálu?
Extracelulárn&i= acute;
signál
Inaktivní
Ras
GDP
Aktivní
Ras
GTP
=
=
=
GTP
GDP
.
Extracelulární
signál ovlivňuje stav Ras proteinu
2.
Ras protein je aktivován fosforylací vazby GDP a inaktivován defosforylací vazby <= /b>  GTP
<= span style=3D'mso-special-format:lastCR;display:none'>
P
3.
Aktivní Ras protein přenáší signál do jádra  ® MAP-kinázy
GTP
=
=
=
4.
Signál reguluje transkripci genů aktivních při = buněčném = dělení
TRANSKRIPCE
=
Bu= něčné dělení
5.
Buněčné dělení probíhá v kontrolované podobě
Ras<= /b>
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=
7
Protoonkogen c-ras – str. 145 (výs= ledek)
Bodová mutace – substituce U®G (viz genetický kód, str. 83)
Extracelulárn&i= acute;
signál
Inaktivní
Ras
GDP
Aktivní
Ras
GTP
=
=
=
GTP
GDP
 
Ras protein je stále aktivní - nedocház&iac= ute;
k hydrolýze GTP na GDP
 
Aktivní Ras protein stále přenáší signál = do jádra  
GTP
=
=
=
 
Tento signál nepřetržitě <= span style=3D'position:absolute;top:66.0%;left:76.77%;width:16.47%;height:3.0%'= >podněcuje transkripci genů regulujících  buněčné dělení
TRANSKRIPCE
=
 Buněčné dělení probíhá
v nekontrolované podobě=
Ras<= /b>
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8
Protoonkogen c-ras
– komentář
&#= 344;ešení:
c-ras se normálně inaktivuje hydrolýzou GT= P na GDP
Některé mutace v c-ras znemožní inaktivaci nebo vedou  k aktivitě c-ras bez vazby k G= TP
Produkt je protein, který váž= ;e nukleotid nesoucí guanin =
Asociace s receptorem, který se váže s různými růstovými faktory
Po aktivaci receptoru je uvolněn GDP <= /span>vázaný k c-ras a naváže se GTP
GTP aktivuje c-ras, ten předá signál fosforylací Raf – první v kaskádě MAP-kináz
Tato signální dráha vede v jádře k aktivaci transkripčních faktorů nebo genů časné odpovědi jako např. c-myc
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/joAA+jO++6+9w7878IHT/zwxheP/PHKJ8/88s43D/3z0kdP/fTWV4/98QUAADs= ------=_NextPart_01C95CB3.BAD78E40 Content-Location: file:///C:/A4236E38/onko_cz08_soubory/slide0096.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="us-ascii" Onkogenetika
9
Tumor-supresorové geny
MUTACE V TUMOR-SUPRESOROVÝCH GENECH = ;
<= /span> RECESIVNÍ CHARAKTER
JEDNA MUTOVANÁ ALELA MŮŽE BÝT ZDĚDĚNA
AUTOSOMÁLNĚ DOMINATN&Iacu= te; TYP DĚDIČNOSTI
DĚDÍ SE PREDISPOSICE<= /b>
Sporadický výskyt nádorového onemocnění= ;: dvě somatické mutace, výskyt odpovídá frekvenci onemocnění v populaci
Fami= liární výskyt: 1. mutace zárodečná, 2. somatická
predisposice, časný vznik nádorů, multifokální nebo bilaterální výskyt, v&iacu= te;ce členů rodiny má stejný typ nádoru <= /span>
<= span style=3D'font-size:75%'>Hypot&e= acute;za dvou zásahů (Knudson)
<= span style=3D'font-size:75%'>Ztr&aac= ute;ta vrozené heterozygozity (LOH) – vazebná analýza&= #13;
<= span style=3D'font-size:75%'>např= ;. gen pro esterázu D (marker) je ve vazbě s genem Rb1
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10
Tumor-supresorové geny – příčiny ztráty funkce
<= span style=3D'font-size:75%'>Delece – mohou postihnout různé části genu =
<= span style=3D'font-size:75%'>Mitotic= ká nondisjunkce
<= span style=3D'font-size:75%'>Mitotic= ká rekombinace
Uniparentální disomie (oba chromo= somy jsou původem od jednoho z rodičů)
<= span style=3D'font-size:75%'>Bodov&a= acute; mutace
<= span style=3D'font-size:75%'>Inaktiv= ace produktu (vyvázání virovým antigenem) =
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11
Lokalizace nádoru
Gen
Chromosom
Mechanismus
působení
o= 9;i (retinoblastom), kosti, prsa, plíce, močový měchýř, prostata
Rb1
13q14
Regulace buněčn&eac= ute;ho cyklu
ledvi= ny a další orgány (WAGR syndrom)
WT1/WT2
11p13
Regulace buněčn&eac= ute;ho cyklu
různé= ; typy nádorů (cca 50% všech nádorů mutace TP53)
TP53
17p13
tlusté střevo (familiární adenoma-tózní polypóza), žaludek, nedě-dičné = kolorektální karcinomy
APC
5q21
Regulace hladiny β-kateninu, buněčné proliferac= e a adheze =
prsa, ovaria, prostata, larynx, zažívací trakt, pankreas
BRCA1
BRCA2
17p21
13q12-q13
Chybný repair <= /span>dvouvláknových zlomů DNA
Tumor-supresorové geny – vybran&ea= cute; příklady
Pozastavení cyklu v G1&= #13;
 - transkripční faktor<= /span>
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13
=
Tumor-supresorové geny
– vybrané příklady:   RB1
Retinobl= astom – nádor očí
Vě= tšinou výskyt u dětí
V&yacut= e;skyt sporadický – 2 somatické mutace; unilaterální, 60% pacientů
Famili&= aacute;rní výskyt –
=      40% pacientů -  1.mutace z&aacut= e;rodečná,  2. somatická; <= /span>bilater= ální onemocnění
Mutace o= bou genů na homologních chromosomech=   jsou nezbytné pro manifestaci nádorové choroby<= /b>
druhá mutace
somatická
děděná = predisposice
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14
Retinoblastom – str. 142
Velikost = fragmentů (kb)
pacient s bilaterálním
retinoblastome= m
pacient s unilaterálním
retinoblastome= m
=
normáln= í
fibroblasty
fibroblasty
fibroblasty
 tumor
 tumor
&#= 13;
=
=
=
=
=
=
=
7,5
5,3
9,8
6,2
9,8
7,5
5,3
6,2
Restrikční mapa
=
Hybridizace (Southern blot) s DNA normálních jedinců a s DNA pacientů
s jednostranným nebo oboustranným retinoblastomem
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file:///C:/A4236E38/onko_cz08_soubory/slide0130.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="us-ascii" Onkogenetika
15
pacient s bilaterálním
retinoblastome= m
pacient s unilaterálním
retinoblastome= m
=
Restrikční mapa
Velikost = fragmentů (kb)
normální = ;
fibroblasty
fibroblasty
fibroblasty
 tumor
 tumor
&#= 13;
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=
=
=
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7,5
5,3
9,8
6,2
9,8
7,5
5,3
6,2
=
7,5
5,3
9,8
6,2
7,5
5,3
9,8
6,2
7,5
5,3
9,8
6,2
6,2
Zárodečná mutace
6,2
Somatická mutace
7,5
5,3
7,5
Dvě somatické mutace
FIBROBLASTY
RETINOBLASTOM
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= 226;Při familiárním výskytu nádoru prsu nebo prsu a ovarií jsou v genetickém poradenství využívány dva tumor-supresorové geny BRCA1 (breast cancer 1) a BRCA2 (breast cancer 2) =
Produkty obou genů BRCA tvoří komplexy s produkty dalších genů a podílejí se tak na regulaci průběhu buněčného cyklu a při rep= airu DNA
Děděná mutace BRCA1 se vyskytuje u žen v rodinách s familiárním výskytem nádoru prsu, ovarií anebo prsu a ovarií
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Zárodečná mutace genu BRCA2 je asociována s výskytem nádoru prsu u žen i mužů; u mužů tak&eacut= e; se vznikem nádoru prostaty, pankreatu a s Fanconiho anémií
Tumor-supresorové geny BRCA1, BRCA2
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Příklad familiárního výskytu nádorů asociovaných s mutací genu BRCA2
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Nádor prsu
Nádor prsu
Nádor prsu
Nádor prsu
Nádor prsu
Nádor prsu
Nádor slinivky
Nádor prostaty
Nádor žaludku= a prostaty
Nádor prsu
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Sporadický a familiární výskyt nádoru prsu v populaci žen
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19
   Alely        = ;   Matka      Otec        Dcera        = ;  Nádor prsu dcery
        = ;            &n= bsp;            = ;            &n= bsp;            = ;            &n= bsp;            = ;            &n= bsp;            = ;            &n= bsp;            = ;            &n= bsp; 
+
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2
1
Vazebná analýza marke= r genu s genem BRCA1
- str. 143-1= 44
BRCA1+/+
BRCA1+
Delece, mitotická nondisjunkce …. =
BRCA1-
BRCA1-
BRCA1+
BRCA1-
BRCA1-, např. substituce
Vyšetřovan= é buňky matky, otce, dcery: fibroblasty nebo leukocyty <= /div>
Ztráta heterozygozity (LOH)
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20
Familiární výsk= yt nádoru prsu a ovárií ̵= 1; str. 144 (rodokmenová = studie)
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Celoživotní riziko =
dcera IV/2: 80% ( nosička mutace)
dcera IV/3: populační, cca 10%
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21
Mutátorové geny (geny mismatch re= pairu)
hMSH2, hML= H1, hPMS1, hPMS2, hMSH6, hMSH3
Kontrola stability buněčného genomu
Opravy chybného párování bází (při replikaci)
Mutace MMR genů se ve fenotypu projevuj&iacut= e; nestabilitou délky mikrosatelitních lokusů (př. CAn) = ;
Mutace MMR zvyšují frekvenci mutací v genomu 100 –1000x =
Mutace MMR mají recesivní charakter
AD dědičnost nádorového onemocnění
Lynchů= ;v syndrom I –nádory tlustého střeva a rekta
Lynchův syndrom II - kolorektáln&iacut= e; karcinomy, a u 30% pacientů nádory endometria, žaludku, slinivky, močov&eac= ute;ho traktu
3D9711gen7
MMR geny rozpoznají původn&iacut= e; vlákno DNA, které má methylované = = některé báze – oprava na novém vláknu
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22
<= span style=3D'mso-special-format:nobullet;display:none'>•Nenáhodné (primární)
Filadelfský chromosom (Ph1) = ;
<= nobr>Translokace – Burkittův lymfom
<= nobr>Amplifikace, double-minutes
<= span style=3D'mso-special-format:nobullet;display:none'>•Náhodné (sekundární)
Nepravidelně se vyskytující chromosomální  přestavby (náhodné delece, translokace, dicentrické chromosomy, prstencové chromosomy, isochromosomy ….)
<= nobr>Heterogenní počet chromosomů, např. pseudodiploidní
Chromosom= ální nálezy v nádorových bu= 28;kách
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23
Náhodné = chromosom&= aacute;lní nálezy v nádorových bu= 28;kách
3Drin60
Prstencový (ring) chromosom
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24
Náhodné chromosom&= aacute;lní nálezy v nádorových bu= 28;kách
        = ;            &n= bsp;            = ; 
isochromosom –= příklad str. 146
3Diso1 3Diso2 3Diso60
Protoonkogen erbA je lokalizovaný na chromosomu 17q
Kóduje vazebnou doménu receptoru glukokortikoidu a = estrogenu ® navýšení
Na p raménku chromo= somu 17 je lokalizovaný tumor-supresorový gen TP53
V isochromosomu i(17)q není přítomen ® vliv na regulaci buněčného cyklu
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25
Nenáhodné chromosom&= aacute;lní nálezy
Burkittův = lymfom
Tra= nslokace protoonkogenu c-myc [např. t(8;= 14)] vede ke zvýšené transkripci genu;
jeho produkt je transkripční faktor pro geny, které kontrolují buněčnou proliferaci = ;
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Nenáhodné= ; chromosom&= aacute;lní nálezy – Burkitt&= #367;v lymfom <= /span>
= Nejčastěji translokace t(8;14),
ale i t(2;= 8), t(8;= 22)
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file:///C:/A4236E38/onko_cz08_soubory/slide0139.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="us-ascii" Onkogenetika
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Nenáhodná chromosomáln&iac= ute; aberace
Chronick&aacut= e; myeloidní leukemie (CML)
Filadelfsk&yac= ute; chromosom (Ph) <= /span>
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<= ![endif]>
28
Chronická myeloidní leukemie (CML)
Filadelfsk&yacu= te; chromosom (Ph) <= /span>
Filadelfský (Ph) chromosom - reciprok&a= acute; translokace mezi ch= romosomem 9 a 22 - { t(9;22)(q34;q11) }
Cytogenetický prognostický marke= r u 90% případů chronické myeloidní leukemie (CML)
Cytogenetický marker u 5 -20%případů akutní lymfocytární = leukemie (ALL) 
Translokace ® = fuzní gen  BCR-ABL, zlom v BCR ("breakpoint c= luster region") genu na chromosomu 22 a ABL protoonkogenu = (Abelsonova leukemie – v-onc) na chromos= omu 9
Produkt fuzního genu je onkoprotein 210= kD, má transformační schopnosti
Fuzní gen BCR-ABL ®<= /b> výsledek fuze buď exonu 1-2 BCR g= enu nebo exonu 1-3 BCR genu s exonem 2 genu ABL
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29
Nenáhodná chromosomální aberace
Amplifikace - protoonkogen N-myc<= /span>
Amp= lifikace sekvence DNA
A) homogenně zbarvené oblasti (HSR)
B) samostatné útvary - double minutes
•<= /span>diagnostický a prognostický = marker
•<= /span>rodina protoonkogenů myc (virus myeloblastózy kuřat) regulace buněčného cyklu =
•<= /span>N-myc – neuroblastom
•<= /span>L-myc – malobuněčné karcinomy plic
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<= ![endif]>
30
Metoda FISH
= 226;Spoje= ní postupů klasické cytogenetiky a technologie molekulární genetiky
= 226;Založena na schopnosti jednovláknové (denaturované) sondy DNA vázat se k cílové sekvenci (princip komplementarity) <= b>
Použití= pro vyšetření chromosomů v mitoze nebo v interfázi
= 226;DNA sond= a je předem označena některým fluorochromem (př. = Texas Re= d, FITC, atd.) <= /b>
= 226;Je možné použít několik typů sond – konkr&eac= ute;tní sondu volíme podle indikace vyšetření
Centromerické sondy<= /span>: tvořeny a-satelit= ními sekvencemi repetitivní DNA přítomné v oblasti centromery ® rychlá= ; detekce numerických aberací, zejména v nedělících se = buň= kách
Lokus= -specifické sondy: vá= ží se specificky na vybrané místo (lokus) = na chromosomu ® stanovení někter= ých = struktur= álních změn (mikrodeleční syndromy, specifické translokace u některých malignit atp.)
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31
Metoda FISH
•<= /span>Celoc= hromosomové sondy (malovací)
Připraveny jako směs fragmentů DNA konkrétního chromosomu
Po jejich aplikaci dojde k “obarvení” celého chromoso= mu
Používají= se pro určení některých strukturálních aberací, jako jsou translokace, inserce nebo komplexní přestavby (hlavně v buňkách nádor$= 7;), a dále pro stanovení původu nadpo= 69;etných marker- nebo ring-chromosomů
Tyto sondy vyžaduj&iacu= te; chromosomy v metafázi, pro interf&a= acute;zní jádra je nelze použít
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32
 
Mnohobarevná malovací sonda – karyotyp nádor= 3;
(hyperdiploidní počet chromosomů + přestavby)
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33
 
Lokus-specifická interfázní sonda ná= ;dor p<= b>rsu
Protoonkogen Her-2/neu kóduje receptor = pro epidermální růstový = faktor s tyrosinkinázovou aktivitou
Centromera – zelený signál    Her-2/neu – červený signál)
2x zelený signál   v obou interfázn&iac= ute;ch jádrech =3D přítomnost páru homologních  chromosomů (na obou snímcích)
Her-2/neu – červený sign&aac= ute;l: 2x ve zdravé tkáni (na každém chromosomu 1x), ale 7x v buňce nádoru, tzn. 6x amplifikovaný gen na jenom chrom= osomu)
<= b>Amplifikace genu Her-2/neu - prognostický a diagnostický marker u karcinomů prsu
 i dalších nádor= ů (např. nádory močového měchýře
Charakterizujte rozdílnost signálů v buňkách.
Jaký typ metody FISH byl použit?
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34

Amplifikace protoonkogenu L-myc=
malobuně&#= 269;ný karcinom plic
•= metoda FISH
•= mnohočetné kopie protoonkogenu L- myc
•= nepříznivá prognóza&= #13;
•<= /span>mnohonásobná amplifikace tvoří „oblak“,  jednotlivé signály jsou nesnadno detekovatelné
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Chromosomá= lní přestavby v buňkách nádoru prsu
Chromosomy buněk <= span style=3D'font-size:167%;color:#FF3300'>nádoru prsu
Mnohočetné náhodné strukturní přestavby
Nádor prsu – amplifikace protoonkogenu Her-2/neu &#= 13;
Ve většině nádorových buněk (mnoho signálů tvoří = “oblak”)
Nenáhodná chromosomální přestavba
Karyotyp charakterizuje závažnost onemocnění, naznačuje prognózu, = je = vodítkem pro volbu terapi= e
Detekce Her-2/neu metodo= u FISH
Stanovte, kte= rý = vzorek představuje náhodné, který nenáhodné chromosomální aberace.
Multicolor FISH
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36
Komparativní genomická hybridizace (CGH)
CGH - molekulární cytogenetická metoda
Identifikuje mnohočetné chromosomální nebalancované přestavby v nádorových buňkách, = nedetekuje balancované přestavby&#= 13;
Patologická změna musí být nejméně v 50% buněk = ;
Genomická DNA zdravé a DNA nádorové tkáně - simultánní in situ hybridizace s normálními chromos= omy v metafázi
Detekce probami – pro DNA nádoru zelená fluorescence, DNA zdravé tkáně (kontrolní DNA) červená fluorescence&= #13;
Poměr intensity těchto dvou fluorescenčních signálů udává míru r= ozdílu mezi vzorkem DNA isolované ze zdravých a nádorových buněk
Hodnocení fluorescenčních signálů vyžaduje zařízení pro kvantitativní vyhodnocení fluorescenčního signálu
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Komparativní genomická hybridizace (CGH)
3D"cgh_abn"
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document.onkeydown =3D _KDH; document.ondragstart=3DCancel document.onselectstart=3DCancel self.focus() } function Redirect( frmId ) { var str=3Ddocument.location.hash,idx=3Dstr.indexOf('#'), sId=3DGetSldId() if(idx>=3D0) str=3Dstr.substr(1); if( window.name !=3D frmId && ( sId !=3D str) ) { obj =3D GetObj("Main-File") window.location.href=3Dobj.href+"#"+sId return 1 } return 0 } var MHTMLPrefix =3D CalculateMHTMLPrefix(); function CalculateMHTMLPrefix() { if ( document.location.protocol =3D=3D 'mhtml:') { href=3Dnew String(document.location.href) Start=3Dhref.indexOf('!')+1 End=3Dhref.lastIndexOf('/')+1 if (End < Start) return href.substring(0, Start) else return href.substring(0, End) } return ''; } function GetTags(base,tag) { if(g_supportsPPTHTML) return base.all.tags(tag); else return base.getElementsByTagName(tag); } function UpdNtsPane(){ if(frames["PPTNts"]) PPTNts.location.replace( MHTMLP= refix+GetHrefObj( gCurSld ).mNtsHref ) } function UpdNavPane( sldIndex ){ if(gNavLoaded) 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FULLSCR_HREF = : FULLSCR_HREF+"#"+GetHrefObj(gCurSld).mSldHref; if(PPTNav.event.ctrlKey) { var w =3D (window.screen.availWidth * 1.0) / 2.0 var h =3D w * (PPTSld.g_origH * 1.0) / PPTSld.g_origW win =3D window.open( MHTMLPrefix+href,null,"toolbar=3D0,resizable=3D1,top= =3D0,left=3D0," + "width=3D"+ w + ",height=3D" + h ); if( win.document.body && PPTSld.g_animUseRuntime ) win.document.body.PPTSldFrameset=3Dwindow; } else { win =3D window.open( MHTMLPrefix+href,null,"fullscreen=3Dyes" ); if( win.document.body && PPTSld.g_animUseRuntime ) win.document.body.PPTSldFrameset=3Dwindow; } } function ToggleVNarration() { rObj=3DPPTSld.document.all("NSPlay") if( rObj && !PPTSld.g_animUseRuntime ) { if( (rObj.playState =3D=3D 1)||(rObj.playState =3D=3D 0) ) rObj.Play() else if( rObj.playState =3D=3D 2 ) rObj.Pause() else return; } else if( PPTSld.g_animUseRuntime ) { narObj =3D PPTSld.document.all("narrationID") if( narObj ) narObj.togglePause() } } function GetCurSldNum() { obj=3DGetHrefObj(gCurSld) if( obj.mOrigVis =3D=3D 1 ) return obj.mSldIdx else return gCurSld } function GetNumSlds() { if( GetHrefObj(gCurSld).mOrigVis =3D=3D 1 ) return GetSldList().mNumVisSlds; else return GetSldList().mList.length } function GetSldNum( href ) { for(ii=3D0; ii 1 ) PopSldList(); else if( !IsFramesMode() ) { if( gLoopCont ) GoToFirst() else EndShow() } } function GoToPrevSld() { ii=3DgCurSld-1 if( ii > 0 ) { obj=3DGetHrefObj(ii) while ( obj && ( obj.mVis =3D=3D 0 ) && ( ii>0 ) ) obj=3DGetHrefObj(--ii) if( ii =3D=3D 0 ) ii=3D1 GoToSldNum(ii) } } function GoToFirst(){ GoToSld( GetHrefObj(1).mSldHref ) } function GoToLast() { ii=3DGetSldList().mList.length if( ii !=3D gCurSld ) GoToSld( GetHrefObj(ii).mSldHref ) } function GoToSldNum( num ) { if( PPTSld.event ) PPTSld.event.cancelBubble=3Dtrue obj =3D GetHrefObj( num ) obj.mVis=3D1 gPrevSld=3DgCurSld gCurSld =3D num; PPTSld.location.replace(MHTMLPrefix+obj.mSldHref) if( IsFramesMode() ) { UpdNavPane(); UpdOtlPane(); UpdNtsPane() } } function GoToSld( href ) { if( PPTSld.event ) PPTSld.event.cancelBubble=3Dtrue GetHrefObj( GetSldNum(href) ).mVis=3D1 PPTSld.location.replace(MHTMLPrefix+href) } function SldUpdated( id ) { if( id =3D=3D GetHrefObj(gCurSld).mSldHref ) return gPrevSld=3DgCurSld gCurSld=3DGetSldNum(id) if( IsFramesMode() ) { UpdNavPane(); UpdOtlPane(); UpdNtsPane() } } function PrevSldViewed(){ GoToSld( GetHrefObj(gPrevSld).mSldHref ) } function HasPrevSld() { return ( gIsEndShow || ( gCurSld !=3D 1 && GetHrefO= bj( gCurSld-1 ).mVis =3D=3D 1 )||( GetCurSldNum() > 1 ) ) } function HasNextSld() { return (GetCurSldNum() !=3D GetNumSlds()) } function CloseWindow() { if( HideMenu() ) return; var event =3D PPTSld.event; if( !IsFramesMode() && event && (event.keyCode=3D=3D27 || event.keyCode=3D= =3D32 || event.type=3D=3D"click" ) ) window.close( self ); CatchNumKeys( self, event ); } function Unload() { gIsEndShow=3D0; } function SetupEndShow() { gIsEndShow=3D1; PPTSld.document.body.scroll=3D"no"; PPTSld.document.onkeypress=3DCloseWindow; PPTSld.document.onclick=3DCloseWindow; PPTSld.document.oncontextmenu=3D_CM; } function EndShow() { if( IsFramesMode() ) return if( PPTSld.event ) PPTSld.event.cancelBubble=3Dtrue doc=3DPPTSld.document var dir =3D doc.body.dir if( dir !=3D "rtl" ) dir =3D "ltr"; doc.open() doc.writeln('


' + ENDSHOW_MESG + '

') doc.close() } function SetSldVisited(){ GetSldList().mList[gCurSld-1].mVisited=3Dtrue } function IsSldVisited(){ return GetSldList().mList[gCurSld-1].mVisited } function hrefList( sldHref, visible, advDelay, advClk ) { this.mSldHref=3D this.mNtsHref =3D sldHref this.mOrigVis=3D this.mVis =3D visible this.mVisited=3D false this.mAdvDelay=3D advDelay this.mAdvOnClk=3D advClk } function SldList(arr,curSld,fEnd) { this.mCurSld =3D curSld; this.mList =3D new Array(); var idx =3D 1; for(ii=3D0;ii 0) { PushSldList(sldList,fEnd); gCurSld =3D 1; } else if( PPTSld.event ) PPTSld.event.cancelBubble=3Dtrue } function PushSldList(arr,fEnd) { var ii =3D gSldStack.length; gSldStack[ii] =3D new SldList(arr,gCurSld,fEnd); GoToSld( gSldStack[ii].mList[0].mSldHref ); } function PopSldList() { if (gSldStack[gSldStack.length-1].fEndShow) EndShow() else { gCurSld =3D gSldStack[gSldStack.length-1].mCurSld; gSldStack[gSldStack.length-1] =3D null; gSldStack.length--; var sldList =3D gSldStack[gSldStack.length-1]; GoToSld( sldList.mList[gCurSld - 1].mSldHref ); } } var custShowList=3Dnew Array(); function ImgBtn( oId,bId,w,action ) { var t=3Dthis t.Perform =3D _IBP t.SetActive =3D _IBSetA t.SetInactive=3D _IBSetI t.SetPressed =3D _IBSetP t.SetDisabled=3D _IBSetD t.Enabled =3D _IBSetE t.ChangeIcon =3D null t.UserAction =3D action t.ChgState =3D _IBUI t.mObjId =3D oId t.mBorderId=3D bId t.mWidth =3D w t.mIsOn =3D t.mCurState =3D 0 } function _IBSetA() { if( this.mIsOn ) { obj=3Dthis.ChgState( gHiliteClr,gShadowClr,2 ) obj.style.posTop=3D0 } } function _IBSetI() { if( this.mIsOn ) { obj=3Dthis.ChgState( gFaceClr,gFaceClr,1 ) obj.style.posTop=3D0 } } function _IBSetP() { if( this.mIsOn ) { obj=3Dthis.ChgState( gShadowClr,gHiliteClr,2 ) obj.style.posLeft+=3D1; obj.style.posTop+=3D1 } } function _IBSetD() { obj=3Dthis.ChgState( gFaceClr,gFaceClr,0 ) obj.style.posTop=3D0 } function _IBSetE( state ) { var t=3Dthis GetObj( t.mBorderId ).style.visibility=3D"visible" if( state !=3D t.mIsOn ) { t.mIsOn=3Dstate if( state ) t.SetInactive() else t.SetDisabled() } } function _IBP() { var t=3Dthis if( t.mIsOn ) { if( t.UserAction !=3D null ) t.UserAction() if( t.ChangeIcon ) { obj=3DGetObj(t.mObjId) if( t.ChangeIcon() ) obj.style.posLeft=3Dobj.style.posLeft+(t.mCurState-4)*t.mWidth else obj.style.posLeft=3Dobj.style.posLeft+(t.mCurState-0)*t.mWidth } t.SetActive() } } function _IBUI( clr1,clr2,nextState ) { var t=3Dthis SetBorder( GetObj( t.mBorderId ),clr1,clr2 ) obj=3DGetObj( t.mObjId ) obj.style.posLeft=3Dobj.style.posLeft+(t.mCurState-nextState)*t.mWidth-obj= .style.posTop t.mCurState=3DnextState return obj } function TxtBtn( oId,oeId,action,chkState ) { var t=3Dthis t.Perform =3D _TBP t.SetActive =3D _TBSetA t.SetInactive=3D _TBSetI t.SetPressed =3D _TBSetP t.SetDisabled=3D _TBSetD t.SetEnabled =3D _TBSetE t.GetState =3D chkState t.UserAction =3D action t.ChgState =3D _TBUI t.mObjId =3D oId t.m_elementsId=3D oeId t.mIsOn =3D 1 } function _TBSetA() { var t=3Dthis if( t.mIsOn && !t.GetState() ) t.ChgState( gHiliteClr,gShadowClr,0,0 ) } function _TBSetI() { var t=3Dthis if( t.mIsOn && !t.GetState() ) t.ChgState( gFaceClr,gFaceClr,0,0 ) } function _TBSetP() { if( this.mIsOn ) this.ChgState( gShadowClr,gHiliteClr,1,1 ) } function _TBSetD() { this.ChgState( gFaceClr,gFaceClr,0,0 ) this.mIsOn =3D 0 } function _TBSetE() { var t=3Dthis if( !t.GetState() ) t.ChgState( gFaceClr,gFaceClr,0,0 ) else t.ChgState( gShadowClr,gHiliteClr,1,1 ) t.mIsOn =3D 1 } function _TBP() { var t=3Dthis if( t.mIsOn ) { if( t.UserAction !=3D null ) t.UserAction() if( !t.GetState ) return if( t.GetState() ) t.SetPressed() else t.SetActive() } } function _TBUI( clr1,clr2,lOffset,tOffset ) { SetBorder( GetObj( this.mObjId ),clr1,clr2 ) Offset( GetObj( this.m_elementsId ),lOffset,tOffset ) } function Offset( obj, top, left ){ obj.style.top=3Dtop; obj.style.left=3Dle= ft } function SetBorder( obj, upperLeft, lowerRight ) { s=3Dobj.style; s.borderStyle =3D "solid" s.borderWidth =3D 1 s.borderLeftColor =3D s.borderTopColor =3D upperLeft s.borderBottomColor=3D s.borderRightColor =3D lowerRight } function GetBtnObj(){ return gBtnArr[window.event.srcElement.id] } function BtnOnOver(){ b=3DGetBtnObj(); if( b !=3D null ) b.SetActive() } function BtnOnDown(){ b=3DGetBtnObj(); if( b !=3D null ) b.SetPressed() } function BtnOnOut(){ b=3DGetBtnObj(); if( b !=3D null ) b.SetInactive() } function BtnOnUp() { b=3DGetBtnObj() if( b !=3D null ) b.Perform() else Upd() } function GetNtsState(){ return parent.gNtsOpen } function GetOtlState(){ return parent.gOtlOpen } function GetOtlTxtState(){ return parent.gOtlTxtExp } function NtsBtnSetFlag( fVal ) { s=3Ddocument.all.item( this.m_flagId ).style s.display=3D"none" if( fVal ) s.display=3D"" else s.display=3D"none" } function _BSetA_Border(){ b =3D gBtnArr[this.mObjId]; if( b !=3D null ) b.S= etActive() } function _BSetI_Border(){ b =3D gBtnArr[this.mObjId]; if( b !=3D null ) b.S= etInactive() } function _BSetP_Border(){ b =3D gBtnArr[this.mObjId]; if( b !=3D null ) b.S= etPressed() } function _BSetA_BorderImg() { b =3D gBtnArr[this.mBorderId] if( b !=3D null && this.mIsOn && !b.GetState() ) { obj=3Dthis.ChgState( gHiliteClr,gShadowClr,2 ) obj.style.posTop=3D0 } } function _BSetI_BorderImg() { b =3D gBtnArr[this.mBorderId] if( b !=3D null && this.mIsOn && !b.GetState() ) { obj=3Dthis.ChgState( gFaceClr,gFaceClr,1 ) obj.style.posTop=3D0 } } var gHiliteClr=3D"THREEDHIGHLIGHT",gShadowClr=3D"THREEDSHADOW",gFaceClr=3D"= THREEDFACE" var gBtnArr =3D new Array() gBtnArr["nb_otl"] =3D new TxtBtn( "nb_otl","nb_otlElem",parent.ToggleOtlPan= e,GetOtlState ) gBtnArr["nb_otlElem"] =3D new TxtBtn( "nb_otl","nb_otlElem",parent.ToggleOt= lPane,GetOtlState ) gBtnArr["nb_nts"] =3D new ImgBtn( "nb_nts","nb_ntsBorder",10,parent.ToggleN= tsPane ) gBtnArr["nb_nts"].SetActive =3D _BSetA_BorderImg; gBtnArr["nb_nts"].SetInactive =3D _BSetI_BorderImg; gBtnArr["nb_ntsBorder"] =3D new TxtBtn( "nb_ntsBorder","nb_ntsElem",parent.= ToggleNtsPane,GetNtsState ) gBtnArr["nb_ntsElem"] =3D new TxtBtn( "nb_ntsBorder","nb_ntsElem",parent.To= ggleNtsPane,GetNtsState ) gBtnArr["nb_prevBorder"] =3D gBtnArr["nb_prev"]=3D new ImgBtn( "nb_prev","n= b_prevBorder",30,parent.GoToPrevSld ) gBtnArr["nb_nextBorder"] =3D gBtnArr["nb_next"]=3D new ImgBtn( "nb_next","n= b_nextBorder",30,parent.GoToNextSld ) gBtnArr["nb_sldshw"]=3D new ImgBtn( "nb_sldshw","nb_sldshwBorder",18,parent= .FullScreen ) gBtnArr["nb_sldshwBorder"] =3D new TxtBtn( "nb_sldshw","nb_sldshwBorder",pa= rent.FullScreen,null ) gBtnArr["nb_sldshwBorder"].SetActive =3D _BSetA_Border; gBtnArr["nb_sldshwBorder"].SetInactive =3D _BSetI_Border; gBtnArr["nb_sldshwText"] =3D new TxtBtn( "nb_sldshw","nb_sldshwText",parent= .FullScreen,null ) gBtnArr["nb_sldshwText"].SetActive =3D _BSetA_Border; gBtnArr["nb_sldshwText"].SetInactive =3D _BSetI_Border; gBtnArr["nb_voice"] =3D gBtnArr["nb_voiceBorder"] =3D new ImgBtn( "nb_voice= ","nb_voiceBorder",18,parent.ToggleVNarration ) gBtnArr["nb_otlTxtBorder"] =3D gBtnArr["nb_otlTxt"]=3D new ImgBtn( "nb_otlT= xt","nb_otlTxtBorder",23,parent.ToggleOtlText ) gBtnArr["nb_ntsBorder"].m_flagId=3D "nb_nts" gBtnArr["nb_ntsBorder"].SetFlag =3D NtsBtnSetFlag gBtnArr["nb_otlTxt"].ChangeIcon=3D GetOtlTxtState var sNext=3D"Další",sPrev=3D"Předchozí",sEnd=3D"Kon= ec prezentace",sFont=3D"Arial",sArrow=3D"Šipka",sFreeform=3D"Voln&yacu= te; tvar",sRect=3D"Obdélník",sOval=3D"Ovál" function ShowMenu() { BuildMenu(); var doc=3DPPTSld.document.body,x=3DPPTSld.event.clientX+doc.scrollLeft,y= =3DPPTSld.event.clientY+doc.scrollTop m =3D PPTSld.document.all.item("ctxtmenu") m.style.pixelLeft=3Dx if( (x+m.scrollWidth > doc.clientWidth)&&(x-m.scrollWidth > 0) ) m.style.pixelLeft=3Dx-m.scrollWidth m.style.pixelTop=3Dy if( (y+m.scrollHeight > doc.clientHeight)&&(y-m.scrollHeight > 0) ) m.style.pixelTop=3Dy-m.scrollHeight m.style.display=3D"" } function _CM() { if( !parent.IsFullScrMode() ) return; if(!PPTSld.event.ctrlKey) { ShowMenu() return false } else HideMenu() } function BuildMenu() { if( PPTSld.document.all.item("ctxtmenu") ) return var mObj=3DCreateItem( PPTSld.document.body ) mObj.id=3D"ctxtmenu" mObj.style.visibility=3D"hidden" var s=3DmObj.style s.position=3D"absolute" s.cursor=3D"default" s.width=3D"120px" SetCMBorder(mObj,"menu","black") var iObj=3DCreateItem( mObj ) SetCMBorder( iObj, "threedhighlight","threedshadow" ) iObj.style.padding=3D2 CreateMenuItem( iObj,sNext,M_GoNextSld,M_True ) CreateMenuItem( iObj,sPrev,M_GoPrevSld,M_HasPrevSld ) CreateSeparator( iObj ) CreateMenuItem( iObj,sEnd,M_End,M_True ) mObj.style.visibility=3D"visible" } function Cancel() { window.event.cancelBubble=3Dtrue; window.event.returnVa= lue=3Dfalse } function Highlight() { ChangeClr("activecaption","threedhighlight") } function Deselect() { ChangeClr("threedface","menutext") } function Perform() { e=3DPPTSld.event.srcElement if( e.type=3D=3D"menuitem" && e.IsActive() ) e.Action() else PPTSld.event.cancelBubble=3Dtrue } function ChangeClr( bg,clr ) { e=3DPPTSld.event.srcElement if( e.type=3D=3D"menuitem" && e.IsActive() ) { e.style.backgroundColor=3Dbg e.style.color=3Dclr } } function M_HasPrevSld() { return( parent.HasPrevSld() ) } function M_GoNextSld() { if( gIsEndShow ) M_End(); 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 Po= známky
Prezentac= e
Osnova
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