Molecular Genetic Analysis of 103 Sporadic Colorectal Tumours in Czech Patients 英文参考文献.docVIP
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Molecular Genetic Analysis of 103 Sporadic Colorectal Tumours in Czech Patients 英文参考文献
MolecularGeneticAnalysisof103SporadicColorectal
TumoursinCzechPatients
PeterVasovcak1*,KristynaPavlikova1,ZdenekSedlacek1,PetrSkapa2,MartinKouda3,JiriHoch3 ,Anna
Krepelova1
1Department of Biology and Medical Genetics, Charles University 2nd Faculty of Medicine and University Hospital Motol, Prague, Czech Republic, 2Department of
PathologyandMolecularMedicine,CharlesUniversity2ndFacultyofMedicineandUniversityHospitalMotol,Prague,CzechRepublic,3DepartmentofSurgery,Charles
University2ndFacultyofMedicineandUniversityHospitalMotol,Prague,CzechRepublic
Abstract
TheCzechRepublichasoneofthehighestincidencesofcolorectalcancer(CRC)inEurope.Toevaluatewhethersporadic
CRCsinCzechpatientshavespecificmutationalprofilesweanalysedsomaticgeneticchangesinknownCRCgenes(APC,
KRAS,TP53, CTNNB1, MUTYHand BRAF,loss ofheterozygosity (LOH) atthe APC locus,microsatellite instability (MSI),and
methylation of the MLH1 promoter) in 103 tumours from 102 individuals. The most frequently mutated gene was APC
(68.9%oftumours),followedbyKRAS(31.1%),TP53(27.2%),BRAF(8.7%)andCTNNB1(1.9%).HeterozygousgermlineMUTYH
mutationsin2patientswereunlikelytocontributetothedevelopmentoftheirCRCs.LOHattheAPClocuswasfoundin
34.3%oftumours,MSIin24.3%andMLH1methylationin12.7%.Seventumours(6.9%)werewithoutanychangesinthe
genestested.TheanalysisyieldedseveralfindingspossiblyspecificfortheCzechcohort.SomaticAPCmutationsdidnot
clusterinthemutationclusterregion(MCR).TumourswithMSIbutnoMLH1methylationshowedearlieronsetandmore
severemutationalprofilescomparedtoMSItumourswithMLH1methylation.TP53mutationswerepredominantlylocated
outsidethehotspots,andtransitionswereunderrepresented.OuranalysissupportstheobservationthatgermlineMUTYH
mutationsarerareinCzechindividualswithsporadicCRCs.Ourfindingssuggesttheinfluenceofspecificethnicgenetic
factorsand/orlifestyleanddietaryhabitstypicalfortheCzechpopulationonthedevelopmentofthesecancers.
Citation: Vasovcak P, Pavlikova K, Sedlacek Z, Skapa P, Kouda M, et al. (2011) Molecular Genet
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