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001     182724
005     20240229145728.0
024 7 _ |a 10.1038/s41586-022-05425-2
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024 7 _ |a pmc:PMC9668746
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024 7 _ |a 0028-0836
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024 7 _ |a 1476-4687
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037 _ _ |a DKFZ-2022-02877
041 _ _ |a English
082 _ _ |a 500
100 1 _ |a Lomakin, Artem
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245 _ _ |a Spatial genomics maps the structure, nature and evolution of cancer clones.
260 _ _ |a London [u.a.]
|c 2022
|b Nature Publ. Group
336 7 _ |a article
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520 _ _ |a Genome 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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588 _ _ |a Dataset connected to CrossRef, PubMed, , Journals: inrepo02.dkfz.de
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a Carcinoma, Intraductal, Noninfiltrating
|2 MeSH
650 _ 2 |a Mutation
|2 MeSH
650 _ 2 |a Genomics
|2 MeSH
650 _ 2 |a Clonal Evolution: genetics
|2 MeSH
650 _ 2 |a Clone Cells
|2 MeSH
650 _ 2 |a Breast Neoplasms: genetics
|2 MeSH
650 _ 2 |a Tumor Microenvironment: genetics
|2 MeSH
700 1 _ |a Svedlund, Jessica
|b 1
700 1 _ |a Strell, Carina
|b 2
700 1 _ |a Gataric, Milana
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700 1 _ |a Shmatko, Artem
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700 1 _ |a Rukhovich, Gleb
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700 1 _ |a Park, Jun Sung
|0 0000-0001-7149-6769
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700 1 _ |a Ju, Young Seok
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700 1 _ |a Dentro, Stefan
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700 1 _ |a Kleshchevnikov, Vitalii
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700 1 _ |a Vaskivskyi, Vasyl
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700 1 _ |a Li, Tong
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700 1 _ |a Bayraktar, Omer Ali
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700 1 _ |a Pinder, Sarah
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700 1 _ |a Richardson, Andrea L
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700 1 _ |a Santagata, Sandro
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700 1 _ |a Campbell, Peter J
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700 1 _ |a Russnes, Hege
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700 1 _ |a Gerstung, Moritz
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700 1 _ |a Nilsson, Mats
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700 1 _ |a Yates, Lucy R
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773 _ _ |a 10.1038/s41586-022-05425-2
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