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

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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