Spatial genomics maps the structure, nature and evolution of cancer clones

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dc.contributor.authorLomakin, Artemko
dc.contributor.authorSvedlund, Jessicako
dc.contributor.authorStrell, Carinako
dc.contributor.authorGataric, Milanako
dc.contributor.authorShmatko, Artemko
dc.contributor.authorRukhovich, Glebko
dc.contributor.authorPark, Jun Sungko
dc.contributor.authorJu, Young Seokko
dc.contributor.authorDentro, Stefanko
dc.contributor.authorKleshchevnikov, Vitaliiko
dc.contributor.authorVaskivskyi, Vasylko
dc.contributor.authorLi, Tongko
dc.contributor.authorBayraktar, Omer Aliko
dc.contributor.authorPinder, Sarahko
dc.contributor.authorRichardson, Andrea L.ko
dc.contributor.authorSantagata, Sandroko
dc.contributor.authorCampbell, Peter J.ko
dc.contributor.authorRussnes, Hegeko
dc.contributor.authorGerstung, Moritzko
dc.contributor.authorNilsson, Matsko
dc.contributor.authorYates, Lucy R.ko
dc.date.accessioned2022-11-30T01:00:35Z-
dc.date.available2022-11-30T01:00:35Z-
dc.date.created2022-11-28-
dc.date.created2022-11-28-
dc.date.issued2022-11-
dc.identifier.citationNATURE, v.611, no.7936, pp.594 - 602-
dc.identifier.issn0028-0836-
dc.identifier.urihttp://hdl.handle.net/10203/301320-
dc.description.abstractGenome sequencing of cancers often reveals mosaics of different subclones present in the same tumour(1-3). Although these are believed to arise according to the principles of somatic evolution, the exact spatial growth patterns and underlying mechanisms remain elusive(4,5). Here, to address this need, we developed a workflow that generates detailed quantitative maps of genetic subclone composition across whole-tumour sections. These provide the basis for studying clonal growth patterns, and the histological characteristics, microanatomy and microenvironmental composition of each clone. The approach rests on whole-genome sequencing, followed by highly multiplexed base-specific in situ sequencing, single-cell resolved transcriptomics and dedicated algorithms to link these layers. Applying the base-specific in situ sequencing workflow to eight tissue sections from two multifocal primary breast cancers revealed intricate subclonal growth patterns that were validated by microdissection. In a case of ductal carcinoma in situ, polyclonal neoplastic expansions occurred at the macroscopic scale but segregated within microanatomical structures. Across the stages of ductal carcinoma in situ, invasive cancer and lymph node metastasis, subclone territories are shown to exhibit distinct transcriptional and histological features and cellular microenvironments. These results provide examples of the benefits afforded by spatial genomics for deciphering the mechanisms underlying cancer evolution and microenvironmental ecology.-
dc.languageEnglish-
dc.publisherNATURE PORTFOLIO-
dc.titleSpatial genomics maps the structure, nature and evolution of cancer clones-
dc.typeArticle-
dc.identifier.wosid000882576600006-
dc.identifier.scopusid2-s2.0-85141627276-
dc.type.rimsART-
dc.citation.volume611-
dc.citation.issue7936-
dc.citation.beginningpage594-
dc.citation.endingpage602-
dc.citation.publicationnameNATURE-
dc.identifier.doi10.1038/s41586-022-05425-2-
dc.contributor.localauthorJu, Young Seok-
dc.contributor.nonIdAuthorLomakin, Artem-
dc.contributor.nonIdAuthorSvedlund, Jessica-
dc.contributor.nonIdAuthorStrell, Carina-
dc.contributor.nonIdAuthorGataric, Milana-
dc.contributor.nonIdAuthorShmatko, Artem-
dc.contributor.nonIdAuthorRukhovich, Gleb-
dc.contributor.nonIdAuthorPark, Jun Sung-
dc.contributor.nonIdAuthorDentro, Stefan-
dc.contributor.nonIdAuthorKleshchevnikov, Vitalii-
dc.contributor.nonIdAuthorVaskivskyi, Vasyl-
dc.contributor.nonIdAuthorLi, Tong-
dc.contributor.nonIdAuthorBayraktar, Omer Ali-
dc.contributor.nonIdAuthorPinder, Sarah-
dc.contributor.nonIdAuthorRichardson, Andrea L.-
dc.contributor.nonIdAuthorSantagata, Sandro-
dc.contributor.nonIdAuthorCampbell, Peter J.-
dc.contributor.nonIdAuthorRussnes, Hege-
dc.contributor.nonIdAuthorGerstung, Moritz-
dc.contributor.nonIdAuthorNilsson, Mats-
dc.contributor.nonIdAuthorYates, Lucy R.-
dc.description.isOpenAccessN-
dc.type.journalArticleArticle-
dc.subject.keywordPlusCARCINOMA IN-SITU-
dc.subject.keywordPlusINVASIVE BREAST-CANCER-
dc.subject.keywordPlusLYMPH-NODE METASTASIS-
dc.subject.keywordPlusSINGLE-CELL-
dc.subject.keywordPlusHETEROGENEITY-
dc.subject.keywordPlusPROGRESSION-
dc.subject.keywordPlusMUTATION-
dc.subject.keywordPlusTISSUE-
dc.subject.keywordPlusMODEL-
dc.subject.keywordPlusDCIS-
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