biostudies-literatureFunnell TCancer Research UKNCI NIH HHS106-115https://www.ebi.ac.uk/biostudies/studies/S-EPMC9712114biostudies-literatureUnknown612(7938)How cell-to-cell copy number alterations that underpin genomic instability¹ in human cancers drive genomic and phenotypic variation, and consequently the evolution of cancer², remains understudied. Here, by applying scaled single-cell whole-genome sequencing³ to wild-type, TP53-deficient and TP53-deficient;BRCA1-deficient or TP53-deficient;BRCA2-deficient mammary epithelial cells (13,818 genomes), and to primary triple-negative breast cancer (TNBC) and high-grade serous ovarian cancer (HGSC) cells (22,057 genomes), we identify three distinct 'foreground' mutational patterns that are defined by cell-to-cell structural variation. Cell- and clone-specific high-level amplifications, parallel haplotype-specific copy number alterations and copy number segment lenNatureSingle-cell genomic variation induced by mutational processes in cancer.PMC9712114K99 CA256508P30 CA008748Grewal DGreenwood WMoore RAShah SPPham JCeglia NLim JLPBiele JWilliams EUhlitz FAlon SFunnell TWalton NALiu YFO'Flanagan CHAbrams DGonzalez-Fernandez CVan Vliet MWassie ATBruna AEirew PBattistoni GIMAXT ConsortiumZamarin DBurger MKaragiannis EDGrimaldo FZheng PXu Hde Algara TRFisher ELlanos VCBoyden ESShea AWeiner ACQosaj FMiller NCasbolt HTietscher SLee MHannon GJLee HBeatty SRoth AZaikova EDouglas JMFan JChornay NRueda OMHuntsman DGKabeer FBalasubramanian SMcPherson ABodenmiller BCaldas CPearson IBojilova VCui YEyal-Lubling YBrimhall JLee SRSawicka KShi HYap DZhang AWSinha AHavasov EWang BMulvey CMJoyce JAWeigelt BWatson SSAparicio SGonzalez-Solares EASalehi SMasud TKim SHAu VDinh KNTavare SXia CLaks EVogl SLDa Cruz Paula AKuett LNugent FMartin SDLi YJauset CMcKinney SEmenari ALai DRibes MPGoodwin DRVazquez-Garcia IBecker RWild SADariush AReis-Filho JSWilliams MJKovacevic TYoldas AKSepulveda LABressan DKunes RAl Sa'd MMcAlpine JNWindhager JHarris OCannell IGSmith AHarris SZhuang XTing JLeventhal ECallari MLerda GRusk NLeung SfalseSingle-cell genomic variation induced by mutational processes in cancer.How cell-to-cell copy number alterations that underpin genomic instability¹ in human cancers drive genomic and phenotypic variation, and consequently the evolution of cancer², remains understudied. Here, by applying scaled single-cell whole-genome sequencing³ to wild-type, TP53-deficient and TP53-deficient;BRCA1-deficient or TP53-deficient;BRCA2-deficient mammary epithelial cells (13,818 genomes), and to primary triple-negative breast cancer (TNBC) and high-grade serous ovarian cancer (HGSC) cells (22,057 genomes), we identify three distinct 'foreground' mutational patterns that are defined by cell-to-cell structural variation. Cell- and clone-specific high-level amplifications, parallel haplotype-specific copy number alterations and copy number segment len2022-01-01T00:00:00Z2022 Dec2025-04-25T17:14:53.558Z2025-04-06T04:55:03.294ZS-EPMC97121143628934210.1038/s41586-022-05249-0