Download Lexicon for “A.C.T. (Assess, Change, Test) on Molecular Testing”

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