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ID:39102423
大小:1.28 MB
页数:44页
时间:2019-06-24
《FASAY技术在肝癌p53基因突变检测中的应用与其对p53基因突变体显性抑制效应的分析》由会员上传分享,免费在线阅读,更多相关内容在学术论文-天天文库。
1、复旦大学硕士论文Abstract1Usingthefunctionalanalysisofseparateda11elesinyeastFASAYscreenthep53mutationsinlivertumors.Livercanceristhesixthmostcommoncancerworldwide,butbecauseoftheverypoorprognosisitisthethirdmostcormoncauseofdeathfromcancer.Chinaisthecountrywiththehighestinci
2、denceanddeath,bothbeyond50%.WehereestablishthefunctionalanalysisofseDaratedaIielesinyeastF矗SAYtosoreenthep53mutationjnlivereancerandanalysisthecorrelationbetweenthestatusofp53geneandclinicalpathologyandprognosis.Wedetectedthep53mutationsin39outof63primaryHCCsamplesby
3、FASAY.Bysequencingthep53cDNA,19tumorshadp53mutationsat249codon.oneofwhichwasadouble—missensemutation(746.747GC.GC>CG.TA)leadingArgtoThrnotreportedbefore.Inadditjon,wealsofoundthreeframeshiftsandtwoin—framedeletionsnotreDorted.Thenthecorrelationofp53statusandclinicalp
4、ath0109icalfeaturesofthe63HCChadbeentested,andp53statuswasnotsignificantlyassociatedwithDatients’age(P=O.309),tumorsize(P=0.269),grade(P=O.359),pTNM(P=O.194).Howeverwenoticedp53hotspotmutation249”‘isfind6outof8tumorswithdiameterbelow2cm,and249”。mutationwassignificant
5、lyassociatedwjthtuJJ】orsize(P=O.024)an(ipTNM(P=O.004j,butnotage(P=O。144)andgrade(P=0.734).Because249Ⅵ”mutationisanimportant士’actorinheptocarcinogenesisintheareawithAFBlexposure,andourresultsuggestexaminationof249codonmutationfromplasmaofthepeople1ivingintheareawiLhhi
6、ghAFBlexposuremaybesignificantbio—markerfordiagnosisandtreatmentoflivercanceraLearlvstage.2IdentificationdoⅢinantp53叫tantsbyFASAYassayWemodifiedtheADE2一basedyeastD53functionalassayaccordingtoInga.Atoallowstrai譬htforwardcharacterizationofthedominancepoLentialofp53muta
7、nts,andtestedallthemutantswegotfromHCC.Firstlv,a11the【【lutationsareonthecorcbindingdomaln.Theresultshowedallthenonsensemutantswererecessive,sug譬estingthatthetetramerizationdomainwasnecessarvforamutanLtoabrogatewildty口efunction,butin—framcdeletionmutantshaddirrerentph
8、enotypesaccordingtotheirlocationsandsco口esofthemutations.11hemutanLdeleting5aainthemiddIeofL.3100pwasdominanceoverwildtvpep53,复旦人学硕
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