ArticleMulticlonalInvasioninBreastTumorsIdentifiedbyTopographicSingleCellSequencingGraphicalAbstractHighlightsdDevelopmentofaspatiallyresolvedsingle-cellgenomesequencingmethoddInDCIS-IDCbreastcancer,genomicevolutionoccurredpriortoinvasiondInvasioninvolvedtheco-migrationofmultipleclonesintotheadjacenttissuesAuthorsAnnaK.Casasent,AislynSchalck,RuliGao,...,FundaMeric-Bernstam,MaryE.Edgerton,NicholasE.NavinCorrespondencemedgerton@mdanderson.org(M.E.E.),nnavin@mdanderson.org(N.E.N.)InBriefRetainingspatialinformationinsingle-cellanalysisprovidesinsightintoclonalinvasionpatternsanddiseaseprogressioninpatientswithDCIS-IDCbreastcancer.Casasentetal.,2018,Cell172,205–217January11,2018ª2017ElsevierInc.https://doi.org/10.1016/j.cell.2017.12.007ArticleMulticlonalInvasioninBreastTumorsIdentifiedbyTopographicSingleCellSequencingAnnaK.Casasent,1,2AislynSchalck,1,2RuliGao,1EmiSei,1AnnalyssaLong,1WilliamPangburn,1TodCasasent,3FundaMeric-Bernstam,4MaryE.Edgerton,5,*andNicholasE.Navin1,2,3,6,*1DepartmentofGenetics2GraduateSchoolofBiomedicalSciences3DepartmentofBioinformaticsandComputationalBiology4DepartmentofInvestigationalCancerTherapeutics5DepartmentofPathologyTheUniversityofTexasMDAndersonCancerCenter,Houston,TX,USA6LeadContact*Correspondence:medgerton@mdanderson.org(M.E.E.),nnavin@mdanderson.org(N.E.N.)https://doi.org/10.1016/j.cell.2017.12.007SUMMARYDuctalcarcinomainsitu(DCIS)isanearly-stagebreastcancerthatinfrequentlyprogressestoinva-siveductalcarcinoma(IDC).Genomicevolutionhasbeendifficulttodelineateduringinvasionduetoin-tratumorheterogeneityandthelownumberoftumorcellsintheducts.Toovercomethesechallenges,wedevelopedTopographicSingleCellSequencing(TSCS)tomeasuregenomiccopynumberprofilesofsingletumorcellswhilepreservingtheirspatialcontextintissuesections.WeappliedTSCSto1,293singlecellsfrom10synchronouspatientswithbothDCISandIDCregionsinadditiontoexomesequencing.Ourdatarevealadirectgenomiclineagebetweeninsituandinvasivetumorsubpopulationsandfurthershowthatmostmutationsandcopyn...
