Nucleic Acids as Molecular Diagnostics

393 Pages·2014·5.81 MB·English

by  Andreas Keller

Edited by
Andreas Keller and Eckart Meese
Nucleic Acids
as Molecular
Diagnostics

Editedby
AndreasKeller
EckartMeese
NucleicAcidsas
MolecularDiagnostics
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Edited by Andreas Keller and Eckart Meese
Nucleic Acids as Molecular Diagnostics
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V
Contents
ListofContributors XIII
Preface XIX
1 Next-GenerationSequencingforClinicalDiagnostics
ofCardiomyopathies 1
JanHaas,HugoA.Katus,andBenjaminMeder
1.1 Introduction 1
1.2 CardiomyopathiesandWhyGeneticTestingisNeeded 1
1.3 NGS 2
1.4 NGSforCardiomyopathies 2
1.5 SamplePreparation 3
1.6 BioinformaticsAnalysisPipeline 4
1.7 InterpretationofResultsandTranslationintoClinicalPractice 4
References 6
2 MicroRNAsasNovelBiomarkersinCardiovascularMedicine 11
BrittaVogel,HugoA.Katus,andBenjaminMeder
2.1 Introduction 11
2.2 miRNAsareAssociatedwithCardiovascularRiskFactors 12
2.3 miRNAsinCoronaryArteryDisease 13
2.4 miRNAsinCardiacIschemiaandNecrosis 15
2.5 miRNAsasBiomarkersofHeartFailure 19
2.6 FutureChallenges 20
Acknowledgments 20
References 21
3 MicroRNAsinPrimaryBrainTumors:FunctionalImpact
andPotentialUseforDiagnosticPurposes 25
PatrickRothandMichaelWeller
3.1 Background 25
3.2 Gliomas 26
3.2.1 miRNAasBiomarkersinGliomaTissue 28
VI Contents
3.2.2 CirculatingmiRNAasBiomarkers 29
3.3 Meningiomas 30
3.4 PituitaryAdenomas 31
3.5 Medulloblastomas 31
3.6 OtherBrainTumors 32
3.6.1 Schwannomas 32
3.6.2 PCNSLs 33
3.7 SummaryandOutlook 33
References 34
4 GeneticandEpigeneticAlterationsinSporadicColorectalCancer:
ClinicalImplications 39
PawelKarpinski,NikolausBlin,andMariaM.Sasiadek
4.1 Introduction 39
4.2 ChromosomalInstability 40
4.3 MicrosatelliteInstability 43
4.4 DriverSomaticMutationsinCRC 46
4.4.1 APC 46
4.4.2 TP53 47
4.4.3 KRAS 47
4.4.4 BRAF 47
4.4.5 PIK3CA 48
4.4.6 OtherMutations 48
4.5 EpigeneticInstabilityinCRC 48
4.6 Hypomethylation 49
4.7 CpGIslandMethylatorPhenotype 50
4.8 ConcludingRemarks 51
References 51
5 NucleicAcid-BasedMarkersinUrologicMalignancies 63
BerndWullich,PeterJ.Goebell,HelgeTaubert,andSvenWach
5.1 Introduction 63
5.2 BladderCancer 64
5.2.1 HereditaryFactorsforBladderCancer 65
5.2.2 SingleNucleotidePolymorphisms 65
5.2.3 RNAAlterationsinBladderCancer 66
5.2.3.1 FGFR3Pathway 66
5.2.3.2 p53Pathway 67
5.2.3.3 Urine-BasedMarkers 67
5.2.3.4 Serum-BasedMarkers 68
5.2.4 SporadicFactorsforBladderCancer 69
5.2.5 GeneticChangesinNon-InvasivePapillaryUrothelial
Carcinoma 69
5.2.5.1 FGFR3 69
Contents VII
5.2.5.2 ChangesinthePhosphatidylinositol3-KinasePathway 70
5.2.6 GeneticChangesinMuscle-InvasiveUrothelialCarcinoma 72
5.2.6.1 TP53,RB,andCellCycleControlGenes 73
5.2.6.2 OtherGenomicAlterations 74
5.2.7 GeneticAlterationswithUnrecognizedAssociationstoTumorStage
andGrade 75
5.2.7.1 AlterationsofChromosome9 75
5.2.7.2 RASGeneMutations 76
5.3 ProstateCancer 77
5.3.1 HereditaryFactorsforProstateCancer 77
5.3.2 SporadicFactorsforProstateCancer 80
5.3.2.1 PSAandOtherProteinMarkers 80
5.3.2.2 NucleicAcidBiomarkers 81
5.3.3 ProstateCancer:Summary 87
5.4 RenalCellCarcinoma 87
5.4.1 HereditaryFactorsforRCC 87
5.4.2 SporadicFactorsforRCC 90
5.4.2.1 TheOld 90
5.4.2.2 TheNew 91
5.5 Summary 92
References 96
6 FromtheGeneticMake-UptotheMolecularSignature
ofNon-CodingRNAinBreastCancer 129
MichaelG.SchrauderandReinerStrick
6.1 Introduction 129
6.2 MolecularBreastCancerDetection 130
6.2.1 CirculatingFreeDNA 130
6.2.2 LongIntergenicNon-CodingRNA 132
6.2.2.1 HOTAIR 132
6.2.2.2 H19 133
6.2.2.3 GAS5 134
6.2.2.4 LSINCT5 134
6.2.2.5 LOC554202 134
6.2.2.6 SRA1 134
6.2.2.7 XIST 134
6.2.3 NaturalAntisenseTranscripts 135
6.2.3.1 HIF-1a-AS 136
6.2.3.2 H19andH19-AS(91H) 137
6.2.3.3 SLC22A18-AS 137
6.2.3.4 RPS6KA2-AS 137
6.2.3.5 ZFAS1 137
6.2.4 miRNAs 138
6.2.4.1 Tissue-BasedmiRNAProfilinginBreastCancer 138
VIII Contents
6.2.4.2 CirculatingmiRNAs 141
6.3 MolecularBreastCancerSubtypesandPrognostic/Predictive
MolecularBiomarkers 142
References 144
7 NucleicAcid-BasedDiagnosticsinGynecologicalMalignancies 155
SebastianF.M.Häusler,JohannesDietl,andJörgWischhusen
7.1 Introduction 155
7.2 Cervix,Vulva,andVaginalCarcinoma 155
7.2.1 Background 155
7.2.2 RoutineDiagnosticsforHPVInfection 157
7.2.2.1 DigeneHybridCapture2High-RiskHPVDNATest(Qiagen) 158
7.2.2.2 CervistaHPVHR(Holologics) 158
7.2.2.3 cobas4800System(Roche) 159
7.2.2.4 APTIMAHPV(Gen-Probe) 159
7.2.2.5 AbbotRealTimeHighRiskHPVAssay(Abbot) 159
7.2.2.6 PapilloCheckGenotypingAssay(GreinerBioOne) 160
7.2.2.7 INNO-LiPAHPVGenotypingExtra(Innogenetics) 160
7.2.2.8 LinearArray(Roche) 160
7.2.2.9 RecommendationsforClinicalUse 160
7.2.3 Outlook–DNAMethylationPatterns 161
7.3 EndometrialCarcinoma(CarcinomaCorpusUteri) 162
7.3.1 Background 162
7.3.2 RoutineDiagnostics–MicrosatelliteInstability 162
7.3.3 EmergingDiagnostics–miRNAMarkers 163
7.4 OvarianCarcinoma 164
7.4.1 Background 164
7.4.2 RoutineDiagnostics 165
7.4.3 EmergingDiagnostics/Perspective–miRNAProfiling 166
7.5 BreastCancer 167
7.5.1 Background 167
7.5.2 RoutineDiagnostics 168
7.5.2.1 HER2Diagnostics 168
7.5.2.2 GeneExpressionProfiling 169
7.5.2.3 HereditaryBreastCancer/BRCADiagnostics 170
7.5.3 EmergingDiagnostics/Perspectives 173
7.6 Conclusion 175
References 175
8 NucleicAcidsasMolecularDiagnosticsinHematopoietic
Malignancies–ImplicationsinDiagnosis,Prognosis,andTherapeutic
Management 185
JanineSchwambandChristianP.Pallasch
8.1 Introduction 185
8.2 MethodologicalApproaches 186