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Cited by 181

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

Open access
Lomakin, Artem, Svedlund, Jessica, Strell, Carina, Gataric, Milana, Shmatko, Artem, Rukhovich, Gleb, Park, Jun Sung, Ju, Young Seok, Dentro, Stefan, Kleshchevnikov, Vitalii, Vaskivskyi, Vasyl, Li, Tong, Bayraktar, Omer Ali, Pinder, Sarah, Richardson, Andrea L., Santagata, Sandro, Campbell, Peter J., Russnes, Hege, Gerstung, Moritz, Nilsson, Mats, Yates, Lucy R.·2022·Nature

Abstract

Genome 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.

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Metadata

Authors
Lomakin, A., Svedlund, J., Strell, C., Gataric, M., Shmatko, A., Rukhovich, G., Park, J. S., Ju, Y. S., Dentro, S., Kleshchevnikov, V., Vaskivskyi, V., Li, T., Bayraktar, O. A., Pinder, S., Richardson, A. L., Santagata, S., Campbell, P. J., Russnes, H., Gerstung, M., Nilsson, M., & Yates, L. R.
Venue
Nature
Published
2022-11-09
Volume
611
Issue
7936
Pages
594-602
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
OpenAlex
W4308620811
Cited by
181
References
13
FWCI
12.30
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: Spatial genomics maps the structure, nature and evolution of cancer clones. https://app.cochat.ai/papers/10.1038/s41586-022-05425-2
The paper
Lomakin, A., Svedlund, J., Strell, C., Gataric, M., Shmatko, A., Rukhovich, G., Park, J. S., Ju, Y. S., Dentro, S., Kleshchevnikov, V., Vaskivskyi, V., Li, T., Bayraktar, O. A., Pinder, S., Richardson, A. L., Santagata, S., Campbell, P. J., Russnes, H., Gerstung, M., . . . Yates, L. R. (2022). Spatial genomics maps the structure, nature and evolution of cancer clones. Nature. https://doi.org/10.1038/s41586-022-05425-2

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.