Cancer cells ■* INTRODUCTION 1. Most cancers are derived from a single abnormal cell. 2. Cancers are initiated by changes in a cell's DNA sequences. 3. A single mutation is not enough to cause cancer. 4. Tumour progression involves successive rounds of mutation and natural selection. 5. Uncontrolled proliferation. 6. Loss of contact inhibition. 7. Cancerogenous growth often depends on degraded control of differentiation and apoptosis. CYTOGENETIKA Cytogenetika se zabývá studiem chromosomu a jejich abnormalit. Chromosomy se skládají z DNA, histonů a proteinů nehistonové povahy. Každý Chromosom nese několik tisíc genu, které mají svou specifickou funkci v mnoha biologických procesech. Počet lidských chromosomu je 46, z toho 22 typů autozomu a dva typy pohlavních chromosomu. Standardní karyotypování chromosomu pomocí vizualizace G a R pruhů bylo objeveno již v 60. létech. G-pruhování Definition: Technique for producing banding patterns in eukaryotic chromosomes. Bands are produced by staining with Giemsa stain after pretreating chromosomes with trypsin. Each homologous chromosome pair has a unique pattern of g-bands, enabling recognition of particular chromosomes. •G-bands: light, tend to be heterochromatic, late replicating , AT rich •R-bands: reverse to G-bands, dark regions, are euchromatic, GC-rich JI íi 4 5 IP" 1 t 1 1 12 X H K n 1 6 1 7 1 B n U J 2 1 2 2 Y Cytogenetické abnormality: Konstitucionární: Robertsonian translocation: t(13;14) •Trizomie21: lVisomy21 47,XX,+21 Jí íí X 1 2 3 Ií 1 H 6 7 B «IM 4* 5 If ti Tc )J S 10 11 12 11 (( )! 13 14 15 "»I f* n 16 17 18 1* íf 19 20 M. u )} 21 22 XX »Klinefelterův syndrom 49, XXXXY (muži, Xi turn off, ginecomastia, hypogonadismus 'DiGeorge syndrom (delece na dlouhém ramínku HSA 22, kardiatic deffects) Cytogenetické abnormality: Získané: Ph Chromosom Id" Inverze 7<= i! « A U if » n n ti it it u 13 14 15 I* U 16 17 ľf ** 19 2D ****** tí#t B ! * * * r I * \č 1 * * 1 D * 1 * i * * [f 1 *3"; * i ■ 1 ^ jf. 4 I * I Bártova et aL, Figure 3 ti «I Inverze HS A 16 INTER-ARM ISOCHROMATID \NTRACHANGE DELETIONS (SU. NUp. NUd) INTRACHANGES (Incomplete) TERMINAL DELETION MONOCENTRIC TRI RADIAL DICENTR TRIRADIAL INTRAARM INTRACHANGES (Incomplete) INTERSTITIAL DELETION (single minute) INTERCHANGES (SI) INTERCHANGES (Alp, Ad) KEY U nádorových buněk je možné pozorovat řadu genetických abnormalit INTERCHANGE (AC) always both both daughter cells affected '////A one or ŽŽŽŽŽI f\ fragment is, or may be, compound CHROMOSOME-TYPE /*_HSR W^ŕ-^S» ' U-p»« % i A i B C a / ví ,/^ D i E \ • Na F ŕ i a Fluorescence in situ total pmüHAiiotuills to aralyis (lístOíJí) labeled witli biciu total parne iiMimimlffib (control Dl^íWiJ Mih Manin L^^LĹ *^í ** \ (im/