Cancer Driver Genes: Methods and Protocols

216 Pages·2019·6.92 MB·English

by  Timothy K. Starr

Methods in
Molecular Biology 1907
Timothy K. Starr Editor
Cancer
Driver Genes
Methods and Protocols
M M B
ETHODS IN OLECULAR IO LO GY
SeriesEditor
JohnM.Walker
School of Lifeand MedicalSciences
University ofHertfordshire
Hatfield, Hertfordshire,AL109AB,UK
Forfurther volumes:
http://www.springer.com/series/7651
Cancer Driver Genes
Methods and Protocols
Edited by
Timothy K. Starr
Masonic Cancer Center, University of Minnesota Medical School, Minneapolis, MN, USA
Editor
TimothyK.Starr
MasonicCancerCenter
UniversityofMinnesotaMedicalSchool
Minneapolis,MN,USA
ISSN1064-3745 ISSN1940-6029 (electronic)
MethodsinMolecularBiology
ISBN978-1-4939-8966-9 ISBN978-1-4939-8967-6 (eBook)
https://doi.org/10.1007/978-1-4939-8967-6
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Preface
Technologicalandscientificadvanceshaveusheredintheeraofprecisionmedicinewiththe
loftygoalofdeliveringtherighttherapytotherightpatientattherighttime.Torealizethis
goalforcancer therapy,itisimperativethatweunderstandthemolecular underpinningsof
thishighlyheterogeneousandcomplexdisease.IntheUSAtoday,itispredictedthatonein
three people will develop cancer in their lifetime and morbidity due to cancer is only
surpassed, slightly, by heart disease. Developing precise therapies for cancer will require
fundamentalknowledgeconcerningthemolecularchangesthatcausetumorstoform,grow,
and eventually metastasize. Although we have made tremendous strides over the past
hundred years, the complexity of cancer etiology manages to stymie our progress toward
moreeffectivetreatment.
The focus of this Methods in Molecular Biology book is to present protocols for
discovering genetic drivers of cancer. The first chapter presents a brief history of cancer
genediscoveryalongwithadiscussionofcurrenttechniquesforcancergeneidentification.
Theremainingchaptersaredividedintothreemajorparts:Insilicoapproachesusinghuman
sequencedata;invitroapproachesusingcelllinesandorganmodels;andinvivoapproaches
using forward genetic screens in mice. Our hope is that these protocols will be used and
adapted by cancer researchers to expand our knowledge base of molecular mechanisms
contributing to cancer progression. Increased understanding of how cancer cells subvert
healthycellularprocessesandinteractwiththehostorganismwillprovidethefoundationfor
developingprecisetherapiestargetingtherightpatientattherighttime.
Minneapolis,MN,USA TimothyK.Starr
v
Contents
Preface ..................................................................... v
Contributors................................................................. ix
1 CancerGeneDiscovery:PasttoPresent ................................... 1
ChristopherR.Clark,WilaiwanDuRose,andTimothyK.Starr
PART I CANCER GENE DISCOVERY IN SILICO BASED ON SEQUENCING DATA
2 IdentificationofCancerDriverGenesfromaCustomSetofNext
GenerationSequencingData............................................. 19
Shu-HsuanLiuandWei-ChungCheng
3 CancerGeneDiscoverybyNetworkAnalysisofSomaticMutations
UsingtheMUFFINNServer............................................. 37
HeonjongHan,BenLehner,andInsukLee
4 IdentifyingDriverInterfacesEnrichedforSomaticMissenseMutations
inTumors.............................................................. 51
KivilcimOzturkandHannahCarter
5 IdentificationofCancerGenesBasedonDeNovoTransposonInsertion
SiteAnalysisUsingRNAandDNASequencing ............................ 73
AaronSarver
PART II CANCER GENE DISCOVERY USING CELL AND ORGANOID SYSTEMS
6 ACell-BasedMethodforIdentificationofChemotherapy
ResistanceCancerGenes................................................. 83
RaffaeleHellweg,AshleyMooneyham,andMartinaBazzaro
7 EngineeringaBioartificialHumanColonModelThrough
DecellularizationandRecellularization .................................... 91
HuanhuanJoyceChenandMichaelL.Shuler
8 MutagenesisScreensforProstateCancerUsingReplication-Incompetent
LentiviralVectors ....................................................... 103
GrantD.Trobridge
9 ArrayedshRNAScreeningtoIdentifySuppressors
ofAnchorage-IndependentGrowth....................................... 115
UgurEskiocak
10 Genome-WideCRISPR/Cas9ScreeningforIdentification
ofCancerGenesinCellLines ............................................ 125
CharlesH.Adelmann,TimWang,DavidM.Sabatini,andEricS.Lander
11 CRISPR/Cas9-BasedPositiveScreensforCancer-RelatedTraits ............. 137
NicholasJ.Slipek,JyotikaVarshney,andDavidA.Largaespada
vii
viii Contents
12 ExVivoTransposon-MediatedGeneticScreensforCancer
GeneDiscovery......................................................... 145
KathrynA.O’Donnell,YabinGuo,ShruthySuresh,
BarrettL.Updegraff,andXiaorongZhou
PART III CANCER GENE DISCOVERY USING ANIMAL MODELS
13 CancerGeneDiscoveryUtilizingSleepingBeauty
TransposonMutagenesis................................................. 161
KelsieL.Becklin,BrandenA.Smeester,andBrandenS.Moriarity
14 PiggyBacTransposon-BasedInsertionalMutagenesisinMice ................ 171
MathiasJ.Friedrich,IraadF.Bronner,PentaoLiu,
AllanBradley,andRolandRad
15 Liver-SpecificDeliveryofSleepingBeautyTransposonSystem
byHydrodynamicInjectionforCancerGeneValidation..................... 185
AmyP.ChiuandVincentW.Keng
16 EngineeringLargeGenomicRearrangementinMouseEmbryonic
StemCellforCancerGeneDiscovery ..................................... 197
Yuen-YiTsengandAnindyaBagchi
Index ...................................................................... 213
Contributors
CHARLESH.ADELMANN (cid:1) DepartmentofBiology,MassachusettsInstituteofTechnology,
Cambridge,MA,USA;WhiteheadInstituteforBiomedicalResearch,Cambridge,MA,
USA;HowardHughesMedicalInstituteDepartmentofBiology,MassachusettsInstituteof
Technology,Cambridge,MA,USA;DavidH.KochInstituteforIntegrativeCancer
ResearchatMIT,Cambridge,MA,USA
ANINDYABAGCHI (cid:1) TumorInitiationandMaintenanceProgram,SanfordBurnhamPrebys
MedicalDiscoveryInstitute,LaJolla,CA,USA
MARTINABAZZARO (cid:1) DepartmentofObstetrics,GynecologyandWomen’sHealth,University
ofMinnesota,Minneapolis,MN,USA
KELSIEL.BECKLIN (cid:1) DepartmentofPediatrics,UniversityofMinnesota,Minneapolis,MN,
USA;Center forGenomeEngineering,UniversityofMinnesota,Minneapolis,MN,USA;
MasonicCancerCenter,UniversityofMinnesota,Minneapolis,MN,USA;Collegeof
VeterinaryMedicine,UniversityofMinnesota,Minneapolis,MN,USA
ALLANBRADLEY (cid:1) TheWellcomeTrustSangerInstitute,Hinxton,UK
IRAAD F.BRONNER (cid:1) TheWellcomeTrustSangerInstitute,Hinxton,UK
HANNAHCARTER (cid:1) DivisionofMedicalGenetics,DepartmentofMedicine,Universityof
CaliforniaSanDiego,LaJolla,CA,USA;BioinformaticsProgram,Universityof
CaliforniaSanDiego,LaJolla,CA,USA;MooresCancerCenter,UniversityofCalifornia
SanDiego,LaJolla,CA,USA;InstituteforGenomicMedicine,UniversityofCalifornia
SanDiego,LaJolla,CA,USA
HUANHUANJOYCECHEN (cid:1) DepartmentofBiomedicalEngineering,CornellUniversity,
Ithaca,NY,USA;MeyerCancerCenter,WeillCornellMedicine,CornellUniversity,New
York,NY,USA
WEI-CHUNGCHENG (cid:1) GraduateInstituteofBiomedicalSciences,ChinaMedicalUniversity,
Taichung,Taiwan;ResearchCenter forTumourMedicalScience,ChinaMedical
University,Taichung,Taiwan;DrugDevelopmentCenter,ChinaMedicalUniversity,
Taichung,Taiwan
AMYP.CHIU (cid:1) DepartmentofAppliedBiologyandChemicalTechnology,TheHongKong
PolytechnicUniversity,Kowloon,HongKong,China
CHRISTOPHERR.CLARK (cid:1) DepartmentofOb-Gyn&Women’sHealth,Universityof
Minnesota,Minneapolis,MN,USA
WILAIWANDUROSE (cid:1) DepartmentofOb-Gyn&Women’sHealth,UniversityofMinnesota,
Minneapolis,MN,USA
UGURESKIOCAK (cid:1) DepartmentofTranslationalImmunologyandImmunopharmacolgy,
CompassTherapeutics,Cambridge,MA,USA
MATHIASJ.FRIEDRICH (cid:1) TheWellcomeTrustSangerInstitute,Hinxton,UK
YABINGUO (cid:1) GuangdongProvincialKeyLaboratoryofMalignantTumorEpigeneticsand
GeneRegulation,MedicalResearchCenter,SunYat-senMemorialHospital,SunYat-sen
University,Guangzhou,China
HEONJONGHAN (cid:1) DepartmentofBiotechnology,CollegeofLifeScienceandBiotechnology,
YonseiUniversity,Seoul,SouthKorea
ix
x Contributors
RAFFAELEHELLWEG (cid:1) DepartmentofObstetrics,GynecologyandWomen’sHealth,University
ofMinnesota,Minneapolis,MN,USA;HeidelbergUniversityBreastUnit,Heidelberg,
Germany
VINCENTW.KENG (cid:1) DepartmentofAppliedBiologyandChemicalTechnology,TheHong
KongPolytechnicUniversity,Kowloon,HongKong,China
ERICS.LANDER (cid:1) DepartmentofBiology,MassachusettsInstituteofTechnology,Cambridge,
MA,USA;BroadInstituteofMITandHarvard,Cambridge,MA,USA;Departmentof
SystemsBiology,HarvardMedicalSchool,Boston,MA,USA
DAVIDA.LARGAESPADA (cid:1) DepartmentofPediatrics,UniversityofMinnesota,Minneapolis,
MN,USA
INSUKLEE (cid:1) DepartmentofBiotechnology,CollegeofLifeScienceandBiotechnology,Yonsei
University,Seoul,SouthKorea
BENLEHNER (cid:1) EMBL-CRGSystemsBiologyUnit,CentreforGenomicRegulation(CRG),
Barcelona,Spain
SHU-HSUAN LIU (cid:1) GraduateInstituteofBiomedicalSciences,ChinaMedicalUniversity,
Taichung,Taiwan
PENTAOLIU (cid:1) TheWellcomeTrustSangerInstitute,Hinxton,UK
ASHLEY MOONEYHAM (cid:1) DepartmentofObstetrics,GynecologyandWomen’sHealth,
UniversityofMinnesota,Minneapolis,MN,USA
BRANDENS.MORIARITY (cid:1) DepartmentofPediatrics,UniversityofMinnesota,Minneapolis,
MN,USA;Center forGenomeEngineering,UniversityofMinnesota,Minneapolis,MN,
USA;MasonicCancerCenter,UniversityofMinnesota,Minneapolis,MN,USA
KATHRYNA.O’DONNELL (cid:1) DepartmentofMolecularBiology,UTSouthwestern Medical
Center,Dallas,TX,USA;HaroldC.SimmonsComprehensiveCancerCenter,UT
SouthwesternMedicalCenter,Dallas,TX,USA;HamonCenter forRegenerativeScience
andMedicine,UTSouthwesternMedicalCenter,Dallas,TX,USA
KIVILCIMOZTURK (cid:1) DivisionofMedicalGenetics,DepartmentofMedicine,Universityof
CaliforniaSanDiego,LaJolla,CA,USA;BioinformaticsProgram,Universityof
CaliforniaSanDiego,LaJolla,CA,USA
ROLANDRAD (cid:1) DepartmentofMedicineII,KlinikumrechtsderIsar,TechnischeUniversita€t
Mu¨nchen,Munich,Germany;GermanCancerResearchCenter(DKFZ)andGerman
CancerConsortium(DKTK),Heidelberg,Germany
DAVIDM.SABATINI (cid:1) DepartmentofBiology,MassachusettsInstituteofTechnology,
Cambridge,MA,USA;WhiteheadInstituteforBiomedicalResearch,Cambridge,MA,
USA;HowardHughesMedicalInstituteDepartmentofBiology,MassachusettsInstituteof
Technology,Cambridge,MA,USA;DavidH.KochInstituteforIntegrativeCancer
ResearchatMIT,Cambridge,MA,USA;BroadInstituteofMITandHarvard,
Cambridge,MA,USA
AARONSARVER (cid:1) InstituteforHealthInformatics,UniversityofMinnesota,Minneapolis,
MN,USA;MasonicCancerCenter,UniversityofMinnesota,Minneapolis,MN,USA
MICHAELL.SHULER (cid:1) DepartmentofBiomedicalEngineering,CornellUniversity,Ithaca,
NY,USA
NICHOLASJ.SLIPEK (cid:1) DepartmentofPediatrics,UniversityofMinnesota,Minneapolis,MN,
USA
BRANDENA.SMEESTER (cid:1) DepartmentofPediatrics,UniversityofMinnesota,Minneapolis,
MN,USA;Center forGenomeEngineering,UniversityofMinnesota,Minneapolis,MN,
USA;MasonicCancerCenter,UniversityofMinnesota,Minneapolis,MN,USA;Collegeof
VeterinaryMedicine,UniversityofMinnesota,Minneapolis,MN,USA
Contributors xi
TIMOTHYK.STARR (cid:1) DepartmentofOb-Gyn&Women’sHealth,UniversityofMinnesota,
Minneapolis,MN,USA;MasonicCancerCenter,UniversityofMinnesota,Minneapolis,
MN,USA
SHRUTHYSURESH (cid:1) DepartmentofMolecularBiology,UTSouthwestern MedicalCenter,
Dallas,TX,USA
GRANTD.TROBRIDGE (cid:1) PharmaceuticalSciences,WashingtonStateUniversity,Spokane,
WA,USA
YUEN-YITSENG (cid:1) CancerProgram,BroadInstitute,MassachusettesInstituteofTechnology
andHarvardUniversity,Cambridge,MA,USA
BARRETTL.UPDEGRAFF (cid:1) DepartmentofMolecularBiology,UTSouthwesternMedical
Center,Dallas,TX,USA
JYOTIKAVARSHNEY (cid:1) DepartmentofPediatrics,UniversityofMinnesota,Minneapolis,MN,
USA
TIMWANG (cid:1) DepartmentofBiology,MassachusettsInstituteofTechnology,Cambridge,MA,
USA;WhiteheadInstituteforBiomedicalResearch,Cambridge,MA,USA;Howard
HughesMedicalInstituteDepartmentofBiology,MassachusettsInstituteofTechnology,
Cambridge,MA,USA;DavidH.KochInstituteforIntegrativeCancerResearchatMIT,
Cambridge,MA,USA
XIAORONGZHOU (cid:1) DepartmentofMolecularBiology,UTSouthwesternMedicalCenter,
Dallas,TX,USA;DepartmentofImmunology,NantongUniversitySchoolofMedicine,
Nantong,China