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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 1. 2. 3. 4. 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]
