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Lexiconfor“A.C.T.(Assess,Change,Test)on MolecularTesting” (LastreviewedJune2016) Contents Introduction.................................................................................................................................................2 KeyTerms....................................................................................................................................................3 ALK(AnaplasticLymphomaKinase)Gene...............................................................................................3 Alteration.................................................................................................................................................3 Antibody..................................................................................................................................................3 Antigen....................................................................................................................................................3 Biomarker................................................................................................................................................4 EGFR(EpidermalGrowthFactorReceptor).............................................................................................4 Gene........................................................................................................................................................4 GeneExpressionProfile...........................................................................................................................5 GeneticTesting........................................................................................................................................5 Genetics...................................................................................................................................................5 Genome...................................................................................................................................................5 GenomicProfiling....................................................................................................................................6 GenomicSequencing...............................................................................................................................6 Genomics.................................................................................................................................................6 Hereditary................................................................................................................................................6 HereditaryMutation................................................................................................................................7 Kinase......................................................................................................................................................7 KinaseInhibitor........................................................................................................................................7 MolecularMarker....................................................................................................................................7 MolecularTest.........................................................................................................................................8 Molecule..................................................................................................................................................8 Mutation..................................................................................................................................................8 1 Next-GenerationSequencing(NGS)........................................................................................................9 PersonalizedMedicine.............................................................................................................................9 PrecisionMedicine..................................................................................................................................9 Protein...................................................................................................................................................10 ProteinExpression.................................................................................................................................10 SomaticMutation..................................................................................................................................10 TargetedTherapy..................................................................................................................................10 TumorMarker........................................................................................................................................11 TyrosineKinaseInhibitor.......................................................................................................................11 Introduction Thepurposeofthislexiconistodefinecommontermsandphrasesthatappearinthecontextof molecularbiomarkertestinginpatientswithlungcancer.Phraseslike“genomicprofiling”and “moleculartesting”mustbeclearlyunderstoodbymembersofthecancercareteaminorderto facilitatecleardialoguesandcoordinatedmanagementplansforpatientswithlungcancer. Sources: Twomainsourcesofinformationwereusedforthislexicon: • • TheNCIDictionaryofCancerTermsfeatures7,850termsrelatedtocancerandmedicine. http://www.cancer.gov/publications/dictionaries/cancer-terms AmericanCancerSocietyCancerGlossary: http://www.cancer.org/cancer/cancerglossary/index 2 KeyTerms ALK(AnaplasticLymphomaKinase)Gene NCI(Cancer.gov) ACS(Cancer.org) Agenethatmakesaproteincalledanaplastic Notfound lymphomakinase(ALK),whichmaybeinvolvedin cellgrowth.Mutated(changed)formsoftheALK geneandproteinhavebeenfoundinsometypes ofcancer,includingneuroblastoma,non-small celllungcancer,andanaplasticlargecell lymphoma.Thesechangesmayincreasethe growthofcancercells.Checkingforchangesin theALKgeneintumortissuemayhelptoplan cancertreatment.Alsocalledanaplastic lymphomakinasegene.1 Alteration NCI(Cancer.gov) Achangeresultinginsomethingthatisdifferent fromtheoriginal.2 ACS(Cancer.org) Notfound Antibody NCI(Cancer.gov) Aproteinmadebyplasmacells(atypeofwhite bloodcell)inresponsetoanantigen(asubstance thatcausesthebodytomakeaspecificimmune response).Eachantibodycanbindtoonlyone specificantigen.Thepurposeofthisbindingisto helpdestroytheantigen.Someantibodies destroyantigensdirectly.Othersmakeiteasier forwhitebloodcellstodestroytheantigen.An antibodyisatypeofimmunoglobulin.3 ACS(Cancer.org) Aproteinmadebyimmunesystemcellsand releasedintothebloodtohelpdefendthebody againstforeignagents,suchasbacteria.These agentscontaincertainsubstancescalled antigens.Eachantibodyworksagainstone certainantigen. Antigen NCI(Cancer.gov) Anysubstancethatcausesthebodytomakean immuneresponseagainstthatsubstance. Antigensincludetoxins,chemicals,bacteria, viruses,orothersubstancesthatcomefrom ACS(Cancer.org) Asubstancethatcancausethebody’simmune systemtorespondbymakingantibodies.For example,theimmunesystemrespondsto antigensthatarepartofbacteriaandvirusesto 3 outsidethebody.Bodytissuesandcells, includingcancercells,alsohaveantigensonthem thatcancauseanimmuneresponse.These antigenscanalsobeusedasmarkersin laboratoryteststoidentifythosetissuesorcells.4 helppeopleresistinfections.Certaincancercells haveantigensthatcanbefoundbylabtests. Knowledgeoftheseantigenscanbeusedtohelp diagnose,monitor,andeventreatsomecancers. Biomarker NCI(Cancer.gov) Abiologicalmoleculefoundinblood,otherbody fluids,ortissuesthatisasignofanormalor abnormalprocess,orofaconditionordisease.A biomarkermaybeusedtoseehowwellthebody respondstoatreatmentforadiseaseor condition.Alsocalledmolecularmarkerand signaturemolecule.5 ACS(Cancer.org) Referencedas“tumormarker:”Substancesthat canbefoundinthebody(intheblood,urine,or otherbodyfluidsortissues)whenapersonhas cancer.Thesesubstancesareusuallymadeby cancercells,butaresometimesbynormalcellsas well.Differenttypesofcancercanhavedifferent tumormarkers.Forexample,prostate-specific antigen(PSA)isatumormarkerforprostate cancer.Ideally,atumormarkerwouldalwaysbe foundwhenapersonhasacertaintypeof cancer,andwouldneverbefoundifaperson didn’thavecancer.Butinrealitytumormarkers arerarelylikethat,becausenormalcellscan oftenmakethemaswell. EGFR(EpidermalGrowthFactorReceptor) NCI(Cancer.gov) Theproteinfoundonthesurfaceofsomecells andtowhichepidermalgrowthfactorbinds, causingthecellstodivide.Itisfoundat abnormallyhighlevelsonthesurfaceofmany typesofcancercells,sothesecellsmaydivide excessivelyinthepresenceofepidermalgrowth factor.Alsocalledepidermalgrowthfactor receptor,ErbB1,andHER1.6 ACS(Cancer.org) Notfound Gene NCI(Cancer.gov) Thefunctionalandphysicalunitofheredity passedfromparenttooffspring.Genesarepieces ofDNA,andmostgenescontaintheinformation formakingaspecificprotein.7 ACS(Cancer.org) ApieceofDNA(deoxyribonucleicacid)insidea cellthathastheinformationtomakeaspecific protein.Genesareresponsiblefortraitspassed oninfamilies,suchashaircolor,eyecolor,and 4 height,aswellassusceptibilitytocertain diseases. GeneExpressionProfile NCI(Cancer.gov) InformationaboutallmessengerRNAsthatare madeinvariouscelltypes.Ageneexpression profilemaybeusedtofindanddiagnosea diseaseorconditionandtoseehowwellthe bodyrespondstotreatment.Geneexpression profilesmaybeusedinprecisionmedicine.8 ACS(Cancer.org) Notfound GeneticTesting NCI(Cancer.gov) AnalyzingDNAtolookforageneticalteration thatmayindicateanincreasedriskfordeveloping aspecificdiseaseordisorder.9 ACS(Cancer.org) Teststhatcanbedonetoseeifapersonhas certaingenechangesknowntoincreasetherisk ofcancerorotherdiseases.Suchtestingisnot recommendedforeveryone,butforpeoplewith certaintypesoffamilyhistory.Genetic counselingshouldbepartofthegenetictesting process. Genetics NCI(Cancer.gov) Thestudyofgenesandheredity.Heredityisthe passingofgeneticinformationandtraits(suchas eyecolorandanincreasedchanceofgettinga certaindisease)fromparentstooffspring.10 ACS(Cancer.org) Notfound Genome NCI(Cancer.gov) ThecompletesetofDNA(geneticmaterial)inan organism.Inpeople,almosteverycellinthebody containsacompletecopyofthegenome.The genomecontainsalloftheinformationneeded forapersontodevelopandgrow.Studyingthe genomemayhelpresearchersunderstandhow differenttypesofcancerformandrespondto treatment.Thismayleadtonewwaysto diagnose,treat,andpreventcancer.11 ACS(Cancer.org) ThetotalDNA(deoxyribonucleicacid)and sometimesRNA(ribonucleicacid)inasinglecell, representingallofthegeneticinformationofthe organism.Thetermgenomecanalsoreferto certaintypesofgeneticmaterial,suchasthatin thecell’snucleus(nucleargenome)or mitochondria(mitochondrialgenome).Seealso deoxyribonucleicacid,gene,ribonucleicacid. 5 GenomicProfiling NCI(Cancer.gov) ACS(Cancer.org) Alaboratorymethodthatisusedtolearnabout Notfound allthegenesinapersonorinaspecificcelltype, andthewaythosegenesinteractwitheachother andwiththeenvironment.Genomicprofiling maybeusedtofindoutwhysomepeopleget certaindiseaseswhileothersdonot,orwhy peoplereactindifferentwaystothesamedrug. Itmayalsobeusedtohelpdevelopnewwaysto diagnose,treat,andpreventdiseases,suchas cancer.Alsocalledgenomiccharacterization.12 GenomicSequencing NCI(Cancer.gov) Alaboratorymethodthatisusedtodetermine theentiregeneticmakeupofaspecificorganism orcelltype.Thismethodcanbeusedtofind changesinareasofthegenomethatmaybe importantinthedevelopmentofspecific diseases,suchascancer.13 ACS(Cancer.org) Notfound Genomics NCI(Cancer.gov) Thestudyofthecompletegeneticmaterial, includinggenesandtheirfunctions,ofan organism.14 ACS(Cancer.org) Notfound Hereditary NCI(Cancer.gov) Inmedicine,describesthepassingofgenetic informationfromparenttochildthroughthe genesinspermandeggcells.Alsocalled inherited.15 ACS(Cancer.org) Notfound 6 HereditaryMutation NCI(Cancer.gov) ACS(Cancer.org) Agenechangeinabody'sreproductivecell(egg Notfound orsperm)thatbecomesincorporatedintothe DNAofeverycellinthebodyoftheoffspring. Hereditarymutationsarepassedonfromparents tooffspring.Alsocalledgermlinemutation.16 Kinase NCI(Cancer.gov) ACS(Cancer.org) Atypeofenzyme(aproteinthatspeedsup Notfound chemicalreactionsinthebody)thatadds chemicalscalledphosphatestoothermolecules, suchassugarsorproteins.Thismaycauseother moleculesinthecelltobecomeeitheractiveor inactive.Kinasesareapartofmanycell processes.Somecancertreatmentstargetcertain kinasesthatarelinkedtocancer.17 KinaseInhibitor NCI(Cancer.gov) ACS(Cancer.org) Asubstancethatblocksatypeofenzymecalleda Notfound kinase.Humancellshavemanydifferentkinases, andtheyhelpcontrolimportantfunctions,such ascellsignaling,metabolism,division,and survival.Certainkinasesaremoreactiveinsome typesofcancercellsandblockingthemmayhelp keepthecancercellsfromgrowing.Kinase inhibitorsmayalsoblockthegrowthofnew bloodvesselsthattumorsneedtogrow.Some kinaseinhibitorsareusedtotreatcancer.18 MolecularMarker NCI(Cancer.gov) ACS(Cancer.org) Abiologicalmoleculefoundinblood,otherbody Notfound fluids,ortissuesthatisasignofanormalor abnormalprocess,orofaconditionordisease.A molecularmarkermaybeusedtoseehowwell thebodyrespondstoatreatmentforadiseaseor condition.Alsocalledbiomarkerandsignature molecule.19 7 MolecularTest NCI(Cancer.gov) ACS(Cancer.org) Inmedicine,alaboratorytestthatchecksfor Notfound certaingenes,proteins,orothermoleculesina sampleoftissue,blood,orotherbodyfluid. Moleculartestsalsocheckforcertainchangesin ageneorchromosomethatmaycauseoraffect thechanceofdevelopingaspecificdiseaseor disorder,suchascancer.Amoleculartestmaybe donewithotherprocedures,suchasbiopsies,to helpdiagnosesometypesofcancer.Itmayalso beusedtohelpplantreatment,findouthowwell treatmentisworking,ormakeaprognosis.20 Molecule NCI(Cancer.gov) ACS(Cancer.org) Thesmallestparticleofasubstancethathasallof Notfound thephysicalandchemicalpropertiesofthat substance.Moleculesaremadeupofoneor moreatoms.Iftheycontainmorethanoneatom, theatomscanbethesame(anoxygenmolecule hastwooxygenatoms)ordifferent(awater moleculehastwohydrogenatomsandone oxygenatom).Biologicalmolecules,suchas proteinsandDNA,canbemadeupofmany thousandsofatoms.21 Mutation NCI(Cancer.gov) AnychangeintheDNAsequenceofacell. Mutationsmaybecausedbymistakesduringcell division,ortheymaybecausedbyexposureto DNA-damagingagentsintheenvironment. Mutationscanbeharmful,beneficial,orhaveno effect.Iftheyoccurincellsthatmakeeggsor sperm,theycanbeinherited;ifmutationsoccur inothertypesofcells,theyarenotinherited. Certainmutationsmayleadtocancerorother diseases.22 ACS(Cancer.org) AchangeintheDNA(deoxyribonucleicacid)ofa cell.Mostmutationsdonotcausecancer,anda fewmayevenbehelpful.Butalltypesofcancer arethoughttobeduetomutationsthatdamage acell’sDNA.Somecancer-relatedmutationscan bepassedonfromaparent(inherited).This meansthatthepersonisbornwiththemutated DNAinallthebody’scells.Butmostmutations happenafterapersonisborn.Thesearecalled somaticoracquiredmutations.Thistypeof mutationhappensinonecellatatime,andonly 8 Seealso:HereditaryMutation,SomaticMutation affectscellsthatarisefromthesinglemutated cell. Seealso:SomaticMutation Next-GenerationSequencing(NGS) NCI(Cancer.gov) ACS(Cancer.org) Notfound Notfound Othersources: • Second-generationsequencingmethodsthatleadtofaster,high-throughputsequencingof DNAfragmentsinunison.23 • Comparedtotraditionalsequencing,theabilitytofullysequencelargenumbersofgenesina singletestandsimultaneouslydetectdeletions,insertions,copynumberalterations, translocationsandexome-widebasesubstitutionsinknowncancer-relatedgenes.24 PersonalizedMedicine NCI(Cancer.gov) ACS(Cancer.org) Aformofmedicinethatusesinformationabouta Notfound person’sgenes,proteins,andenvironmentto prevent,diagnose,andtreatdisease.Incancer, personalizedmedicineusesspecificinformation aboutaperson’stumortohelpdiagnose,plan treatment,findouthowwelltreatmentis working,ormakeaprognosis.Examplesof personalizedmedicineincludeusingtargeted therapiestotreatspecifictypesofcancercells, suchasHER2-positivebreastcancercells,or usingtumormarkertestingtohelpdiagnose cancer.Alsocalledprecisionmedicine.25 PrecisionMedicine NCI(Cancer.gov) ACS(Cancer.org) Aformofmedicinethatusesinformationabouta Notfound person’sgenes,proteins,andenvironmentto prevent,diagnose,andtreatdisease.Incancer, precisionmedicineusesspecificinformation aboutaperson’stumortohelpdiagnose,plan treatment,findouthowwelltreatmentis working,ormakeaprognosis.Examplesof precisionmedicineincludeusingtargeted therapiestotreatspecifictypesofcancercells, 9 suchasHER2-positivebreastcancercells,or usingtumormarkertestingtohelpdiagnose cancer.Alsocalledpersonalizedmedicine.26 Protein NCI(Cancer.gov) Amoleculemadeupofaminoacids.Proteinsare neededforthebodytofunctionproperly.They arethebasisofbodystructures,suchasskinand hair,andofothersubstancessuchasenzymes, cytokines,andantibodies.27 ACS(Cancer.org) Alargemoleculemadeupofachainofsmaller unitscalledaminoacids.Proteinsservemany vitalfunctionsinsideandoutsideofthebody’s cells. ProteinExpression NCI(Cancer.gov) Referstotheproductionofproteinsbycells.The studyofproteinexpressionincancercellsmay giveinformationaboutaspecifictypeofcancer, thebesttreatmenttouse,andhowwella treatmentworks.28 ACS(Cancer.org) Notfound SomaticMutation NCI(Cancer.gov) AnalterationinDNAthatoccursafter conception.Somaticmutationscanoccurinany ofthecellsofthebodyexceptthegermcells (spermandegg)andthereforearenotpassedon tochildren.Thesealterationscan(butdonot always)causecancerorotherdiseases.29 ACS(Cancer.org) Achange(mutation)inDNA(deoxyribonucleic acid)thatstartsinonecellofthebodyatany timeoflifeafteranembryoisformed.Allthe cellsthatcomefromthatcellwilltypicallyhave thesamemutation,whichinsomecasescanlead tocancer.Thiskindofmutationisdifferentfrom aninheritedmutation,whichispresentatbirth andfoundinallthecellsofthebody.Somatic mutationsarenotpassedontochildren. TargetedTherapy NCI(Cancer.gov) Atypeoftreatmentthatusesdrugsorother substancestoidentifyandattackspecifictypesof cancercellswithlessharmtonormalcells.Some targetedtherapiesblocktheactionofcertain enzymes,proteins,orothermoleculesinvolvedin thegrowthandspreadofcancercells.Other ACS(Cancer.org) Treatmentwithdrugsthatattacksomepartof cancercellsthat’sdifferentfromnormalcells. Targetedtherapiessometimesworkwhen standardchemotherapydrugsdon’t,andthey tendtohavefewersideeffectsthan chemotherapydrugs. 10 typesoftargetedtherapieshelptheimmune systemkillcancercellsordelivertoxicsubstances directlytocancercellsandkillthem.Targeted therapymayhavefewersideeffectsthanother typesofcancertreatment.Mosttargeted therapiesareeithersmallmoleculedrugsor monoclonalantibodies.30 TumorMarker NCI(Cancer.gov) Asubstancefoundintissue,blood,orotherbody fluidsthatmaybeasignofcancerorcertain benign(noncancerous)conditions.Mosttumor markersaremadebybothnormalcellsand cancercells,buttheyaremadeinlargeramounts bycancercells.Atumormarkermayhelpto diagnosecancer,plantreatment,orfindouthow welltreatmentisworkingorifcancerhascome back.ExamplesoftumormarkersincludeCA-125 (inovariancancer),CA15-3(inbreastcancer), CEA(incoloncancer),andPSA(inprostate cancer).31 ACS(Cancer.org) Substancesthatcanbefoundinthebody(inthe blood,urine,orotherbodyfluidsortissues) whenapersonhascancer.Thesesubstancesare usuallymadebycancercells,butaresometimes bynormalcellsaswell.Differenttypesofcancer canhavedifferenttumormarkers.Forexample, prostate-specificantigen(PSA)isatumormarker forprostatecancer.Ideally,atumormarker wouldalwaysbefoundwhenapersonhasa certaintypeofcancer,andwouldneverbefound ifapersondidn’thavecancer.Butinreality tumormarkersarerarelylikethat,because normalcellscanoftenmakethemaswell. TyrosineKinaseInhibitor NCI(Cancer.gov) ACS(Cancer.org) Asubstancethatblockstheactionofenzymes Notfound calledtyrosinekinases.Tyrosinekinasesarea partofmanycellfunctions,includingcell signaling,growth,anddivision.Theseenzymes maybetooactiveorfoundathighlevelsinsome typesofcancercells,andblockingthemmayhelp keepcancercellsfromgrowing.Sometyrosine kinaseinhibitorsareusedtotreatcancer.They areatypeoftargetedtherapy.32 1 http://www.cancer.gov/publications/dictionaries/cancer-terms?CdrID=721252 2 http://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=44643 11 3 http://www.cancer.gov/publications/dictionaries/cancer-terms?CdrID=44918 4 5 http://www.cancer.gov/publications/dictionaries/cancer-terms?CdrID=46086 http://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=45618 6 http://www.cancer.gov/publications/dictionaries/cancer-terms?CdrID=44397 7 8 http://www.cancer.gov/publications/dictionaries/cancer-terms?CdrID=45693 http://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=386201 9 http://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=46128 10 http://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=444994 11 http://www.cancer.gov/publications/dictionaries/cancer-terms?CdrID=44593 12 http://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=561401 13 http://www.cancer.gov/publications/dictionaries/cancer-terms?CdrID=753865 14 http://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=446543 15 http://www.cancer.gov/publications/dictionaries/cancer-terms?CdrID=45983 16 http://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=46365 17 http://www.cancer.gov/publications/dictionaries/cancer-terms?CdrID=641114 18 http://www.cancer.gov/publications/dictionaries/cancer-terms?CdrID=750798 19 http://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=579630 20 http://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=766166 21 http://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=45065 22 http://www.cancer.gov/publications/dictionaries/cancer-terms?CdrID=46063 23 http://www.nature.com/jid/journal/v133/n8/full/jid2013248a.html 24 http://www.ncbi.nlm.nih.gov/pubmed/21657839 25 http://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=561717 26 http://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=741769 12 27 http://www.cancer.gov/publications/dictionaries/cancer-terms?CdrID=46092 28 http://www.cancer.gov/publications/dictionaries/cancer-terms?CdrID=557359 29 http://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=46586 30 http://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=270742 31 http://www.cancer.gov/publications/dictionaries/cancer-terms?CdrID=46636 32 http://www.cancer.gov/publications/dictionaries/cancer-terms?CdrID=44833 13