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Personalizedmolecularclassificationsforhighgradeserousovarian
cancer
LeadInvestigator:
Co Investigator:
PaulPharoah
StrangewaysResearchLaboratories
http://ccge.medschl.cam.ac.uk/dr-paul-pharoah/
JamesBrenton
CambridgeInstitute
http://www.cruk.cam.ac.uk/research-groups/brenton-group
ThisPhDintheOvarianCancerProgrammeprovidesauniqueopportunitytotestmolecular
hypothesesacrosssamplesizesofmorethan2000patientsandtodevelophighthroughput
molecularandimageanalysismethods,includingnext-generationsequencingandRNAprofiling.
ProjectDescription
Highgradeserousovariancarcinoma(HGSOC)isthecommonestformofovariancancerand
mortalityhasnotimprovedoverthepast20yearsdespitelarge-scaletrialsofchemotherapyand
targetedagentsincludingantiangiogenicandPARPinhibitors.Thedefiningmolecularcharacteristics
ofHGSOCaremutationsintumoursuppressorgenes,withfrequentinvolvementofDNArepair
pathways,andextremeDNAstructuralvariation.Howeverincontrasttobreastandothercancers,
robustprognosticmolecularclassificationshavenotbeenidentified.
Thisprojectwillfocusonthe"systemspathology"ofovariancancerusingveryextensiveformalinfixedparaffin-embeddedtissuemicroarrayandgermlinesamplesheldattheStrangewaysResearch
Laboratoryfromlargescalepopulation-basedandclinicaltrialcollections.Wehavepioneeredthe
developmentofnextgenerationsequencing(NGS)foranalysisofFFPEtissuesandinvolvedin
internationalstudiescombiningNGSandNanostringgeneexpressionprofiling.Themainhypothesis
forthisworkisthatcombiningprevalentmolecularandimagephenotypeswithgermlinedataand
outcomeswilluncovermuchmoreaccurateprognosticsignaturestohelpguidepatientcare.
Thisprojectwouldbeidealforcandidateswithastrongnumericalorcomputationalbackground.
Applicationsfromindividualswithabackgroundinmathematics,biostatistics,physicsorcomputer
scienceareparticularlyencouraged.
References
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5.
KöbelM,PiskorzAM,LeeS,LuiS,LePageC,MarassF,etal.Optimizedp53
immunohistochemistryisanaccuratepredictorofTP53mutationinovariancarcinoma.J
Pathol:ClinRes.2016.
PiskorzAM,EnnisD,MacintyreG,GoranovaTE,EldridgeM,Segui-GraciaN,etal.Methanolbasedfixationissuperiortobufferedformalinfornext-generationsequencingofDNAfrom
clinicalcancersamples.Annalsofoncology:officialjournaloftheEuropeanSocietyfor
MedicalOncology/ESMO.2016;27(3):532-9.
KöbelM,MadoreJ,RamusSJ,ClarkeBA,PharoahPD,DeenS,etal.EvidenceforatimedependentassociationbetweenFOLR1expressionandsurvivalfromovariancarcinoma:
implicationsforclinicaltesting.AnOvarianTumourTissueAnalysisconsortiumstudy.British
journalofcancer.2014;111(12):2297-307.
SiehW,KöbelM,LongacreTA,BowtellDD,deFazioA,GoodmanMT,etal.Hormone-receptor
expressionandovariancancersurvival:anOvarianTumorTissueAnalysisconsortiumstudy.
TheLancetOncology.2013;14(9):853-62.
AliHR,IrwinM,MorrisL,DawsonSJ,BlowsFM,ProvenzanoE,etal.Astronomicalalgorithms
forautomatedanalysisoftissueproteinexpressioninbreastcancer.Britishjournalofcancer.
2013;108(3):602-12.
Applications
Toapplyforthisstudentshippleaseseehttp://www.cambridgecancercentre.org.uk/studentships
ForgeneralenquiriespleasecontactTinaThorn [email protected]
Forfurtherinformationorquestionsrelatingtothisprojectpleasecontact:
PaulPharoah [email protected]