Evidence of Genetic Instability in Tumors and Normal Nearby Tissues 英文参考文献.docVIP

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Evidence of Genetic Instability in Tumors and Normal Nearby Tissues 英文参考文献.doc

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Evidence of Genetic Instability in Tumors and Normal Nearby Tissues 英文参考文献

EvidenceofGeneticInstabilityinTumorsandNormal NearbyTissues GiuseppeGeraci1,2,IdaD’Elia1,RosannadelGaudio1,RossellaDiGiaimo1* 1DepartmentofBiologicalSciences,UniversityofNaplesFedericoII,Napoli,Italy,2CeingeBiotecnologieAvanzates.c.ar.l.,Napoli,Italy Abstract Background: Comprehensive analyses have recently been performed on many human cancer tissues, leading to the identificationofanumberofmutatedgenesbutprovidingnoinformationonthevarietyofmutationspresentineachof them.Thisinformationisofinteresttounderstandthepossibleoriginofgenemutationsthatcausetumors. Methodology/PrincipalFindings:WehaveanalyzedthesequenceheterogeneityofthetranscriptsofthehumanHPRTand G6PDsinglecopygenesthatarenotconsideredtumormarkers.Analyseshavebeenperformedondifferentcoloncancers andonthenearbyhistologicallynormaltissuesoftwomalepatients.SeveralcopiesofeachcDNA,whichwereproducedby cloningtheRT-PCR-amplifiedfragmentsofthespecificmRNA,havebeensequenced.Similaranalyseshavebeenperformed onbloodsamplesoftwoostensiblyhealthymalesasreferencecontrols.ThesequenceheterogeneityoftheHPRTandG6PD geneswasalsodeterminedonDNAfromtumortissues.Theemployedanalyticalapproachrevealedthepresenceoflow- frequencymutationsnotdetectablebyotherprocedures.TheresultsshowthatgeneticheterogeneityisdetectableinHPRT andG6PDtranscriptsinbothtumorsandnearbyhealthytissuesofthetwostudiedcolontumors.Similarfrequenciesof mutationsareobservedinpatientgenomicDNA,indicatingthatmutationshaveasomaticorigin.HPRTtranscriptsshow genetic heterogeneity also in healthy individuals, in agreement with previous results on human T-cells, while G6PD transcriptheterogeneityisacharacteristicofthepatienttissues.Interestingly,dataonTP53showlittle,ifany,heterogeneity inthesametissues. Conclusions/Significance:Thesefindingsshowthatgeneticheterogeneityisapeculiaritynotonlyofcancercellsbutalso ofthenormaltissuewhereatumorarises. Citation: Geraci G, D’Elia I, del Gaudio R, Di Giaimo R (2010) Evidence of Genetic Instability in Tumors and Normal Nearby