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@ARTICLE{Lomakin:182724,
      author       = {A. Lomakin$^*$ and J. Svedlund and C. Strell and M. Gataric
                      and A. Shmatko$^*$ and G. Rukhovich$^*$ and J. S. Park$^*$
                      and Y. S. Ju and S. Dentro$^*$ and V. Kleshchevnikov and V.
                      Vaskivskyi and T. Li and O. A. Bayraktar and S. Pinder and
                      A. L. Richardson and S. Santagata and P. J. Campbell and H.
                      Russnes and M. Gerstung$^*$ and M. Nilsson and L. R. Yates},
      title        = {{S}patial genomics maps the structure, nature and evolution
                      of cancer clones.},
      journal      = {Nature},
      volume       = {611},
      number       = {7936},
      issn         = {0028-0836},
      address      = {London [u.a.]},
      publisher    = {Nature Publ. Group},
      reportid     = {DKFZ-2022-02877},
      pages        = {594 - 602},
      year         = {2022},
      note         = {#EA:B450#},
      abstract     = {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.},
      keywords     = {Humans / Female / Carcinoma, Intraductal, Noninfiltrating /
                      Mutation / Genomics / Clonal Evolution: genetics / Clone
                      Cells / Breast Neoplasms: genetics / Tumor Microenvironment:
                      genetics},
      cin          = {B450},
      ddc          = {500},
      cid          = {I:(DE-He78)B450-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:36352222},
      pmc          = {pmc:PMC9668746},
      doi          = {10.1038/s41586-022-05425-2},
      url          = {https://inrepo02.dkfz.de/record/182724},
}