TY  - JOUR
AU  - Lomakin, Artem
AU  - Svedlund, Jessica
AU  - Strell, Carina
AU  - Gataric, Milana
AU  - Shmatko, Artem
AU  - Rukhovich, Gleb
AU  - Park, Jun Sung
AU  - Ju, Young Seok
AU  - Dentro, Stefan
AU  - Kleshchevnikov, Vitalii
AU  - Vaskivskyi, Vasyl
AU  - Li, Tong
AU  - Bayraktar, Omer Ali
AU  - Pinder, Sarah
AU  - Richardson, Andrea L
AU  - Santagata, Sandro
AU  - Campbell, Peter J
AU  - Russnes, Hege
AU  - Gerstung, Moritz
AU  - Nilsson, Mats
AU  - Yates, Lucy R
TI  - Spatial genomics maps the structure, nature and evolution of cancer clones.
JO  - Nature 
VL  - 611
IS  - 7936
SN  - 0028-0836
CY  - London [u.a.]
PB  - Nature Publ. Group
M1  - DKFZ-2022-02877
SP  - 594 - 602
PY  - 2022
N1  - #EA:B450#
AB  - 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.
KW  - Humans
KW  - Female
KW  - Carcinoma, Intraductal, Noninfiltrating
KW  - Mutation
KW  - Genomics
KW  - Clonal Evolution: genetics
KW  - Clone Cells
KW  - Breast Neoplasms: genetics
KW  - Tumor Microenvironment: genetics
LB  - PUB:(DE-HGF)16
C6  - pmid:36352222
C2  - pmc:PMC9668746
DO  - DOI:10.1038/s41586-022-05425-2
UR  - https://inrepo02.dkfz.de/record/182724
ER  -