Journal Article

DKFZ-2022-02877

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Spatial genomics maps the structure, nature and evolution of cancer clones.

Lomakin, A. (First author)DKFZ* ; Svedlund, J. ; Strell, C. ; Gataric, M. ; Shmatko, A.DKFZ* ; Rukhovich, G.DKFZ* ; Park, J. S.DKFZ* ; Ju, Y. S. ; Dentro, S.DKFZ* ; Kleshchevnikov, V. ; Vaskivskyi, V. ; Li, T. ; Bayraktar, O. A. ; Pinder, S. ; Richardson, A. L. ; Santagata, S. ; Campbell, P. J. ; Russnes, H. ; Gerstung, M.DKFZ* ; Nilsson, M. ; Yates, L. R.

2022
Nature Publ. Group London [u.a.]

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Please use a persistent id in citations: doi:10.1038/s41586-022-05425-2

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.

Keyword(s): Humans (MeSH) ; Female (MeSH) ; Carcinoma, Intraductal, Noninfiltrating (MeSH) ; Mutation (MeSH) ; Genomics (MeSH) ; Clonal Evolution: genetics (MeSH) ; Clone Cells (MeSH) ; Breast Neoplasms: genetics (MeSH) ; Tumor Microenvironment: genetics (MeSH)

Note: #EA:B450#

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Contributing Institute(s):

1. Künstl. Intelligenz in der Onkologie (B450)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2022

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Chemical Reactions ; Clarivate Analytics Master Journal List ; Current Contents - Agriculture, Biology and Environmental Sciences ; Current Contents - Life Sciences ; Current Contents - Physical, Chemical and Earth Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 60 ; Index Chemicus ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection ; Zoological Record

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