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000182724 037__ $$aDKFZ-2022-02877
000182724 041__ $$aEnglish
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000182724 1001_ $$0P:(DE-He78)5c386464ccf3e1e1ffa69db986be5be0$$aLomakin, Artem$$b0$$eFirst author$$udkfz
000182724 245__ $$aSpatial genomics maps the structure, nature and evolution of cancer clones.
000182724 260__ $$aLondon [u.a.]$$bNature Publ. Group$$c2022
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000182724 520__ $$aGenome sequencing of cancers often reveals mosaics of different subclones present in the same tumour1-3. Although these are believed to arise according to the principles of somatic evolution, the exact spatial growth patterns and underlying mechanisms remain elusive4,5. 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.
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000182724 650_2 $$2MeSH$$aHumans
000182724 650_2 $$2MeSH$$aFemale
000182724 650_2 $$2MeSH$$aCarcinoma, Intraductal, Noninfiltrating
000182724 650_2 $$2MeSH$$aMutation
000182724 650_2 $$2MeSH$$aGenomics
000182724 650_2 $$2MeSH$$aClonal Evolution: genetics
000182724 650_2 $$2MeSH$$aClone Cells
000182724 650_2 $$2MeSH$$aBreast Neoplasms: genetics
000182724 650_2 $$2MeSH$$aTumor Microenvironment: genetics
000182724 7001_ $$aSvedlund, Jessica$$b1
000182724 7001_ $$aStrell, Carina$$b2
000182724 7001_ $$aGataric, Milana$$b3
000182724 7001_ $$0P:(DE-He78)09d6c35e975cb490a4532eb5b04ccda2$$aShmatko, Artem$$b4$$udkfz
000182724 7001_ $$0P:(DE-He78)5f0460f01de6e6633ab2f2253a8998dc$$aRukhovich, Gleb$$b5$$udkfz
000182724 7001_ $$00000-0001-7149-6769$$aPark, Jun Sung$$b6
000182724 7001_ $$00000-0002-5514-4189$$aJu, Young Seok$$b7
000182724 7001_ $$0P:(DE-He78)40af5fd3ec583f9dc5da1c7c7e00524f$$aDentro, Stefan$$b8$$udkfz
000182724 7001_ $$aKleshchevnikov, Vitalii$$b9
000182724 7001_ $$00000-0002-4080-4965$$aVaskivskyi, Vasyl$$b10
000182724 7001_ $$00000-0002-8240-4476$$aLi, Tong$$b11
000182724 7001_ $$00000-0001-6055-277X$$aBayraktar, Omer Ali$$b12
000182724 7001_ $$00000-0003-4167-8910$$aPinder, Sarah$$b13
000182724 7001_ $$00000-0001-5221-1094$$aRichardson, Andrea L$$b14
000182724 7001_ $$00000-0002-7528-9668$$aSantagata, Sandro$$b15
000182724 7001_ $$00000-0002-3921-0510$$aCampbell, Peter J$$b16
000182724 7001_ $$aRussnes, Hege$$b17
000182724 7001_ $$0P:(DE-He78)bf8843f36606c8735a840f6278fa1e90$$aGerstung, Moritz$$b18$$udkfz
000182724 7001_ $$00000-0001-9985-0387$$aNilsson, Mats$$b19
000182724 7001_ $$00000-0003-4519-7794$$aYates, Lucy R$$b20
000182724 773__ $$0PERI:(DE-600)1413423-8$$a10.1038/s41586-022-05425-2$$gVol. 611, no. 7936, p. 594 - 602$$n7936$$p594 - 602$$tNature <London>$$v611$$x0028-0836$$y2022
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