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

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MARC

Fältnamn	Indikatorer	Metadata
000		04666naa a2200613 4500
001		oai:DiVA.org:su-212292
003		SwePub
008		221206s2022 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
009		oai:DiVA.org:uu-492447
024	7	a https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-2122922 URI
024	7	a https://doi.org/10.1038/s41586-022-05425-22 DOI
024	7	a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4924472 URI
040		a (SwePub)sud (SwePub)uu
041		a engb eng
042		9 SwePub
072	7	a ref2 swepub-contenttype
072	7	a art2 swepub-publicationtype
100	1	a Lomakin, Artem4 aut
245	1 0	a Spatial genomics maps the structure, nature and evolution of cancer clones
264		c 2022-11-09
264	1	b Springer Science and Business Media LLC,c 2022
338		a print2 rdacarrier
520		a Genome sequencing of cancers often reveals mosaics of different subclones present in the same tumour. Although these are believed to arise according to the principles of somatic evolution, the exact spatial growth patterns and underlying mechanisms remain elusive. 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.
650	7	a NATURVETENSKAPx Biologix Genetik0 (SwePub)106092 hsv//swe
650	7	a NATURAL SCIENCESx Biological Sciencesx Genetics0 (SwePub)106092 hsv//eng
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Cancer och onkologi0 (SwePub)302032 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Cancer and Oncology0 (SwePub)302032 hsv//eng
700	1	a Svedlund, Jessicau Stockholms universitet,Institutionen för biokemi och biofysik,Science for Life Laboratory (SciLifeLab)4 aut0 (Swepub:su)jesv4890
700	1	a Strell, Carinau Uppsala universitet,Stockholms universitet,Institutionen för biokemi och biofysik,Science for Life Laboratory (SciLifeLab),Uppsala University, Sweden,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Solna, Sweden4 aut0 (Swepub:uu)carst810
700	1	a Gataric, Milana4 aut
700	1	a Shmatko, Artem4 aut
700	1	a Rukhovich, Gleb4 aut
700	1	a Park, Jun Sung4 aut
700	1	a Ju, Young Seok4 aut
700	1	a Dentro, Stefan4 aut
700	1	a Kleshchevnikov, Vitalii4 aut
700	1	a Vaskivskyi, Vasyl4 aut
700	1	a Li, Tong4 aut
700	1	a Bayraktar, Omer Ali4 aut
700	1	a Pinder, Sarah4 aut
700	1	a Richardson, Andrea L.4 aut
700	1	a Santagata, Sandro4 aut
700	1	a Campbell, Peter J.4 aut
700	1	a Russnes, Hege4 aut
700	1	a Gerstung, Moritz4 aut
700	1	a Nilsson, Matsu Stockholms universitet,Institutionen för biokemi och biofysik,Science for Life Laboratory (SciLifeLab)4 aut0 (Swepub:su)matsn
700	1	a Yates, Lucy R.4 aut
710	2	a Stockholms universitetb Institutionen för biokemi och biofysik4 org
773	0	t Natured : Springer Science and Business Media LLCg 611:7936, s. 594-602q 611:7936<594-602x 0028-0836x 1476-4687
856	4	u https://doi.org/10.1038/s41586-022-05425-2y Fulltext
856	4	u https://uu.diva-portal.org/smash/get/diva2:1724036/FULLTEXT01.pdfx primaryx Raw objecty fulltext:print
856	4 8	u https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-212292
856	4 8	u https://doi.org/10.1038/s41586-022-05425-2
856	4 8	u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-492447

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NATURAL SCIENCES: NATURAL SCIENCES; and Biological Scien ...; and Genetics

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cancer and Oncol ...

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