1、TECHNICA1.SPECIFICATIONISO/TS4425editionFirst2O23-O4Genomicsinformatics-Datae1.ementsandtheirmetadatafordescribingthemicrosate1.1.iteinstabi1.ity(MSI)informationofc1.inica1.massivepara1.1.e1.DNAsequencingInfbrmatiquegnomique-6怙mentsdedonnesetIeursmtadonnespourdicrireIesinformationsre1.ativesinstabi1
2、itdesmicrosate1.1.ites(MSI)dus6quenagemassifpara1.1.i1.ed,ADN1.SOTSRj5c2oOTISO2023COPYRIGHTPROTECTEDDOCUMENTISO2023IUirhM*hedbdi1.iUedotherwiseupdhi.orbmtndH0tf1.ttoni(nc4nmpe*MqnrtiatfifiHipB1.andonnet8CH-1214Vernier,GenevaPhone：M1.22749O1.11觥ftte:丽丽BQrgPub1.ishedinSwitzer1.andContentsForeword1234
3、567.2.2Genera1.B7.32Genera1.7.3.5Subjectofcare97.5Performing107.5.3InformationOn1.ega1.1.yconfirmed107.7 7.6.2statusresu1.tinformation117.8 Recommended11838.3.1infOnnat1.On.13iiiPageIntroductionviScope1Normativereferences1Termsanddefinitions1Abbreviatedterms5Microsate1.1.iteinstabi1.ity(MSI)5Composi
4、tionofe1.ementsfordescribingMSIstatusonc1.inica1.DNANGSreport661Gener3166.2Summarypart7Fie1.dsandtheirnomenc1.atureofrequireddata77.1Genera1.77.2C1.iniedISeqUenCingOrder87.2.1C1.inica1.sequencingordercode7.2.3Dateandtime87.3Infornistiononsubjectofc6.97.3.1Subjectofcareidentifier7kn0rCfrer!，。97.3.4Su
5、bjectofcarebirthdate97.3.67.3.7Referringdiagnosis,107.4Informationon1.ega1.1.yauthorizedpersonorderingc1.inica1.sequencing107.4.1 Genera1.1.aboratory7.4.2 Genera1.107.4.3 Basicinformationonperforming1.aboratory107.5.4 ofreportgeneratorpersononsequencingreport7.6Biospccimeninformation107.6.1 Genera1.
6、10MSITypeofspecimen,7.1,7.2,8.1,8.2,8.377777Genera1.11MSIstatus11Genera1.treatmentModicstioii.11C1.inica1.tria1.information11Fie1.dsandtheirnomenc1.atureofoptiona1.data128.1 Gener2.一.128.2 Referencegenomeinformation12MSIGenera1.8.3.2 CriteriaofMS1.status138.3.3 GenomicpositionfordeterminingMSIstatus
7、138.3.5G1.inuf1.iiaaSiimtiedmitteehasbeenestab1.ishedhastherighttoberepresentedonthatcommittee.Internationa1.organizations,governmenta1.andnongovernmenta1.,in1.iaisonwithISO,a1.sotakepartinthework.ISOco1.1.aboratesc1.ose1.ywiththee1.ectrotechnica1.standardization.Internationa1.E1.ectrotechnica1.Comm
8、ission(IEC)ona1.1.mattersofTheproceduresusedtodeve1.opthisdocumentandthoseintendedforitsfurthermaintenanceareg殿F睽CiMteoSOIECteM槌必得杷油醐解蝴蟠($临酢%COrdanCe朗Fhtheeditoria1.ru1.esoftheSOIECDirectives,Part2(seewww.iso.org/directivcs).AnytradeusedinthisR曲拈OnHggd醐曲Bn捣媲蝴掘网群ns1.雅翩瞰R的阳赧府docf1.旅邮帖由银版subjectofanypa
9、tentrightsidentifiedduringthedeve1.oPmentCfxh。UXuJnMuUU4。beintheIntroductionand/orontheISO1.istofpatentdec1.arationsreceived(secwww.iso.org/patents).constitutenameendorsement,domentisinformationgivenfortheconvenienceofusersanddoesnotForanexp1.anationofthevo1.untarynatureofstandards,themeaningofISOsp
10、ecifictermsand觊版U隅现dwn察脚阳6assE盛ftinwe憎s曲船CnBar池恻Jdead唧乩e盘www.iso.org/iso/foreword.htm1.用i卜称锁/用用P沃edbyTechnica1.CommitteeISO/TC2151.Hea1.thinformatics,SubcommitteeAnyfeedbackorquestionsonthisdocumentshou1.dbedirectedtotheuser*snationa1.standardsbody.Acomp1.ete1.istingofthesebodiescanbefoundIntroducti
11、onMassive1.ypara1.1.e1.sequencingisahigh-throughputana1.ytica1.approachtonuc1.eicacidsequencingthathU。VVbWhO1.eUSedgAnhn1.的JmCaAftDimUMKfcBiddiniCific口iagtod女a空tw8ppJiMhtahMid(pffiePaies.varicnisreS?entStrategiestheconf11)iperforme1.111.ferf1.yy1.te11ronthatmaintainstheactiontoextractcancerce1.1.s.R
12、ecentoutcomesofc1.inica1.tria1.sshowthatthisimmunetherapyisefficientforsomepatientswhohaveaspecificmo1.ecu1.archaracteroftheirtumor三ss.ua,sbWersC4sc1.1H即刑郃曲随她理腼公办“8松1gURCE:ISO25720:2009,4.7DNAsequencingdeterminingtheorderofnuc1.eotidebases(adenine,guanine,cytosineandthymine)inamo1.ecu1.eofDNNote1toe
13、ntry:Sequenceisgenera1.1.ydescribedfromthe5,end.更gURCE:ISO17822:2020.3.19exonepartofthegenomeformedbyexons9URCE:ISO/TS20428:2017.3.13genebasicunitOfheredi1.arymateria1.thatencodesandcontro1.stheexpressionofaproteinorprotein热Unitinde1.insertion(3.9)or/andde1.etion(3.3)EQURCE:ISO/TS20428:2017,3.18inse
14、rtioncontiguousadditionofoneormorebasesintoagenomicsequence史?yRCE:ISO/IEC23092-2:2020,3.18microsate1.1.iterepetitiveDNAe1.ements,a1.soknownassimp1.esequencerepeats(SSR),consistingofshortin1.andemrepeatmotifsofonetoafewnuc1.eotidesthattendtooccurinnon-codingDNofeukaryoticgenomesandthataresometimesref
15、erredtoasvariab1.enumberoftandemrepeats(VNTRs)3.11microsate1.1.iteinstabi1.ityMSig做IatChrepair(MMR)conditionOfgenetichypermutabi1.ity(predispositiontomutation)thatresu1.tsfromimpairedDNADNAmismatchrepairMMRsystemforFecognizingandrepairingerroneousinsertion,de1.etion,andmisincorporationofbasesthat用fj
16、iseduringDNArep1.icationandrecombination,aswe1.1.asrepairingsomeformsofDNAdamagenuc1.eotidemonomerofanuc1.eicacidpo1.ymersuchasDNAorRNANbtehb吨SitiysNucKmD1.iA岫MIgkk1.nSnIjetterSw1.iMSOaIiPmInWs。RNA).4h1.仅灿emi11Muhne;TajertfijrmineDNAorRNAmo1.ecu1.eisgivenbythesequenceofitsnuc1.eotides,whichcanberepr
17、esentedasastringoverthea1.phabet(A?CVG,.T)inthecaseofDNA.andastringoverthea1.phabet(A,.tC.G,U)inthecaseofRNA.Baseswithunknownmo1.ecu1.arcompositionaredenotedwith,N.y9RCE:ISO1EC23092-2:2020,3.20po1.ymerasechainreactionPCRinvitroenzymatictechniquetoincreasethenumberofcopiesofaspecificDNAfragmentbyseve
18、ra1.ordersofmagnitudejSOURCE:ISO16577:2022,3.6.47qua1.ityscorePhredqua1.ityscoreQscoresequencingqua1.ityscoreofagivennuc1.eotidebaseHocetabirtg;eng.definedbythefo1.1.owingequation：Q三-101.og10(e),whereeistheestimatedprobabi1.ityoftheNote2tocntr),:Aqua1.ityScOreof20representsanerrorrateof1in100,withaC
19、OrrcSpondingca1.1.accuracyof99%.Note3toentry：Higherqua1.ityscoresindicateasma1.1.erprobabi1.ity*oferror.1.owerqua1.ityscorescanresu1.tinasignificantportionofthereadsbeingunusab1.e.1.owqua1.ityscoresmaya1.soindicatefa1.se-positivevariantca1.1.s,resu1.tingininaccurateconc1.usions.更9gRCE:ISO20397-2:202
20、1,3.30readtrpetypeofruninthesequencinginstrumentNote1toentry：Itcanbeeithersing1.e-endorpatred-end.Note2toentry：Sing1.e-end：Sing1.ereadrunsthesequencinginstrumentreadsfromoneendofafragmenttotheotherend.NotiiBaQfrmtrjhP*PdStOtdirtttiredendrunsreadfromoneendtotheotherandthenstartsanotherroundofSOURCE:I
21、SO/TS20428:2017,3.27J3.17referencesequencenuc1.eicacidsequencewithbio1.ogica1.re1.evanceNmhint校KyitEiKhRe9rddcHgbqHenCeSingIindted时出GandiniteanhiRiitH11hidiUtE(巧zero.Thecoordinatesysteminthecontextofthisstandardiszero-based(Iejhefirstnuc1.eotidehascoordinate0,anditissaidtobeatposition0)and1.inear1.y
22、increaseswithinthestringfrom1.efttorightRCE:1SO1EC23092-1:2020,3.22readsequencereadfragmentednuc1.eotidesequencesthatareusedtoreconstructtheorigina1.sequencefornext-generationsequencingtechno1.ogies近四RCE:1SOTS20428:2017,3.26variationsequencevariationDNAsequencevariationdifferencesofDNAsequenceamongi
23、ndividua1.sinapopu1.ationRCE:ISO25720:2009,4.8sma1.1.inde1.insertion(3.9)orde1.etion(3.3)of2nuc1.eotidesto100nuc1.eotides2PRCE:1SOTS20428:2017,3.32subjectofcarepersonwhouses,orisapotentia1.userof,ahea1.thcareserviceyg1.RCE:1SOTS22220:2011,3.2,modifiedNotetoentryandsecondpreferredtermde1.eted.targetc
24、apturemethodtocapturegenomicregionsofinterestfromaDNAsamp1.epriortosequencinggpyRCE:ISO/TS20428:2017,3.36targetedsequencingtechniqueusedforsequencingon1.ySeIeCted/targetedgenomicregionsofinterestfromaDNAsamp1.eF2yRCE:ISO/TS22692:2020,3.22,modifiedNotetoentryandsecondpreferredtermde1.eted.who1.eexone
25、sequencingWES里当iqueforsequencingtheexomesoftheprotein-codinggenesinagenomewho1.egenomesequencingWGStechniquethatdeterminesthecomp1.eteDNsequenceofanorganismsgenomeatasing1.etime(SOURCE:ISO/TS20428:2017,3.3944 AbbreviatedtermsCT1.A4CytotoxicT-1.ymphocyteAssociatedProtein4FHIRFastHea1.thcareInteropera
26、bi1.ityResourcesIDMPIdentificationOfMedicinaIProductINNInternationa1.NonproprietaryNamesNCCNNationa1.ComprehensiveCancerNetWOrkNiHNationa1.InstitutesOfHea1.thPD-IProgrammedce1.1.deathprotein1WHOWor1.dHea1.thOrganization5 Microsate1.1.iteinstabi1.ity(MSI)andrepairmismatchesgcncs：dunngDNArep1.ication.
27、PMS2.majorcomponentsfunctionenzymescodedCo1.orecta1.hereditarynon-po1.yposissyndromecancer(HNPCC)rIikeIythemostco1.orecta1.cancerhereditarydifferencesinrnutationorepigeneticinac1.ivationbothre1.atcdtonotaccumu1.ationsyndromesequencesrevea1.cdCancershigh1.yimmunogenictosignatre,inc1.udingoftumorneoan
28、tigenstmor-infi1.trating1.ymphocytes.foundstomach.sma1.1.intestine,pancreas,cancers,tractrandco1.orecta1.,Theendometia1.genomecontainscancersthanATCAnatomica1.TherapeuticChemica1.EBIEuropeanBioinformaticsInstituteH1.7Hea1.th1.eve1.SevenIMPIDInvestigationa1.MP1.DMP1.DMedicina1.ProductIdentiHerNGSNext
29、GenerationSequencingPD-1.1.Programmeddeath-1.igand1SPRECStandardPREanaIyticaICodeUTNUniversa1.Tria1.NumberTheDNAmismatchrepair(MMR)pathwayp1.aysanimportantro1.einthece1.1.cyc1.eprocesstorecognizeforbythefo1.1.owingM1.H1.fMSH2rMSH6rTheandEPCAM.MMRarefourkeydoesn,tworkwhenmutationa1.inactivationinthef
30、ivegenesorepigeneticinactivationoccurs.Itisca1.1.edDeficiencyofmismatchrepair(dMMR).Oneofthemostre1.ateddiseasesis1.ynchsyndrome6.1.ynchsyndrome,a1.soknownascancer.Peop1.ewith1.ynchcoIorecta1.moreistogetcommoncauseofandothercancersatayoungerage(under50).Patientsdeve1.opdMMRtumorsfo1.1.owingtheinacti
31、vationofthesecondwi1.d-typea1.1.e1.ethroughsomaticmutation,1.ossofheterozygosity,orepigeneticsi1.encing.Thesea1.terations-thecaseofcancertype.However,istheon1.y1.ynchofshortbuta1.soofDNArepeatedthroughoutthegenome-specific1.ocationandanincreasedriskofma1.ignanttransformationincertaintissues.Thesetum
32、orshaveahigherfrequencyofsomaticmutationscomparedwithnon-dMMRandandareassumedhave1.argerangeahighproportionof(highmutationburden)Defectivemismatchrepairresu1.tsinahightumormutationburdenandabundantneo-antigenformation,whichcanberecognizedbythehostimmunesystem.Microsate1.1.iteinstabi1.ity(MSI)isthein
33、1.5%to3,5%ofa1.1.humanbi1.iarysuchasureter.humanovarian,andmoreof19mi1.1.ionmicrosate1.1.ites,shorttandemrepeatsofmotifsnf1nuc1.eotideto6nuc1.eotides,typica1.1.yspanning10nuc1.eotidesto60nuc1.eotidesintota1.1.ength7).However,iftheMMRfunctiondoesn,tworkwe1.1.,nuc1.eotideerroraccumu1.ates,especia1.1.y
34、inthehumangenomicposition,inc1.udingmicrosate1.1.ites.8antb!iuHedcefi三rQiiidunv(Qtion.microsate1.1.itescanserveasanindividua1.smo1.ecu1.arbarcode,whichThestatusofMSIisusedasabiomarkerforpredictingtheprognosisOfco1.orecta1.cancerorse1.ecting网睡tsp脸ksbeRM丽确感mimmuneM螂瞄陷院dec1.田园如胆S丽彩械W帼期Ioninhibitors.InMay2017,anewdrug-pembro1.izumab(KEYTRUDA)wasapproved,whichisahumanizedantibodyagainsttheprogrammeddeathreceptor-1(PD-I)1forthetreatmentofpatients限阴醐眼唯触,a11Wi醐曲Iy陈h小城硼酬斛超岫岫既印AarbO的普醐触肿翩礴empwasure搞CIUd雁fi湖险IUm
