Sequential Sequential genetic genetic changes leading to the changes leading to the evolution of colorectal cancer evolution of colorectal cancer hromosome; LOH, loss of heterozygosity hromosome; LOH, loss of heterozygosity deleted in colorectal cancer’; FAP, familial polyposis coli deleted in colorectal cancer’; FAP, familial polyposis coli DNA hypomethylation chr12p chr18q chr17p DNA hypomethylation chr12p chr18q chr17p metastas metastasi AP loss K-ras DCC lo P loss K-ras DCC lo
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Sequential genetic changes leading to the evolution of colorectal cancer
Sequential genetic changes leading to the evolution of colorectal cancer. B.Vogelstein: chr5q DNA hypomethylation chr12p chr18q chr17p metastasis FAP loss K-ras DCC loss p53 other alterations. - PowerPoint PPT Presentation
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Sequential Sequential geneticgenetic changes leading to the changes leading to the evolution of colorectal cancer evolution of colorectal cancer
chr, chromosome; LOH, loss of heterozygositychr, chromosome; LOH, loss of heterozygosityDCC, ‘deleted in colorectal cancer’; FAP, familial polyposis coli DCC, ‘deleted in colorectal cancer’; FAP, familial polyposis coli
B.Vogelstein:B.Vogelstein: chr5q DNA hypomethylation chr12p chr18q chr17p chr5q DNA hypomethylation chr12p chr18q chr17p metastasis metastasis FAP loss K-ras DCC loss p53 FAP loss K-ras DCC loss p53 other alterations other alterations
the formation of the tumor cell requires long timethe formation of the tumor cell requires long timeavg. cell cycle time ~ 28-40 hrsavg. cell cycle time ~ 28-40 hrs
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egér epidermális model: egér epidermális model: kémiai karcinogeneziskémiai karcinogenezis - - soklépcsős modellsoklépcsős modell
DMBADMBA (7,12-dimethyl-benzanthracene)(7,12-dimethyl-benzanthracene): Ha-: Ha-rasras-aktiváló mutáció-aktiváló mutációTPATPA (12-(12-OO-tetradecanoyl-phorbol-13-acetate)-tetradecanoyl-phorbol-13-acetate): cyclin D1 expresszió, papilloma: cyclin D1 expresszió, papillomap53 vesztésp53 vesztés: genom destabilizálása: genom destabilizálásaTGF-betaTGF-beta expresszió: szabályozás kiesik, metasztatikus cc. fejlődés expresszió: szabályozás kiesik, metasztatikus cc. fejlődésE-cadherinE-cadherin: expresszió csökken, könnyebben mozdulnak el a sejtek: expresszió csökken, könnyebben mozdulnak el a sejtek
Accumulation of oncogenic events results in cancerAccumulation of oncogenic events results in cancermultistep processmultistep process
‘‘lucky’ situation: loss of altered cell lucky’ situation: loss of altered cell (purple)(purple) cumulation of mis-regulated functions cumulation of mis-regulated functions (brown)(brown)
etc.etc.
CRC beteg, Dukes-B, nagy tumor, két részlet analíziseCRC beteg, Dukes-B, nagy tumor, két részlet analízise