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Whole-tissue biopsy phenotyping of three-dimensional tumours reveals patterns of cancer heterogeneity
Karolinska Inst, Dept Med Biochem & Biophys, SE-17177 Stockholm, Sweden.;Keio Univ, Dept Urol, Sch Med, Tokyo 1608582, Japan..
Karolinska Inst, Dept Med Biochem & Biophys, SE-17177 Stockholm, Sweden..
Columbia Univ, Dept Biol Sci, New York, NY 10027 USA..
Univ Turku, Turku Ctr Biotechnol, FI-20521 Turku, Finland.;Abo Akad Univ, Fac Sci & Engn, FI-20521 Turku, Finland..
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2017 (English)In: NATURE BIOMEDICAL ENGINEERING, ISSN 2157-846X, Vol. 1, no 10, p. 796-806Article in journal (Refereed) Published
Abstract [en]

Intratumoral heterogeneity is a critical factor when diagnosing and treating patients with cancer. Marked differences in the genetic and epigenetic backgrounds of cancer cells have been revealed by advances in genome sequencing, yet little is known about the phenotypic landscape and the spatial distribution of intratumoral heterogeneity within solid tumours. Here, we show that three-dimensional light-sheet microscopy of cleared solid tumours can identify unique patterns of phenotypic heterogeneity, in the epithelial-to-mesenchymal transition and in angiogenesis, at single-cell resolution in whole formalin-fixed paraffin-embedded (FFPE) biopsy samples. We also show that cleared FFPE samples can be re-embedded in paraffin after examination for future use, and that our tumour-phenotyping pipeline can determine tumour stage and stratify patient prognosis from clinical samples with higher accuracy than current diagnostic methods, thus facilitating the design of more efficient cancer therapies.

Place, publisher, year, edition, pages
Nature Publishing Group, 2017. Vol. 1, no 10, p. 796-806
National Category
Cancer and Oncology
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URN: urn:nbn:se:uu:diva-339722DOI: 10.1038/s41551-017-0139-0ISI: 000418860600001OAI: oai:DiVA.org:uu-339722DiVA, id: diva2:1176552
Available from: 2018-01-22 Created: 2018-01-22 Last updated: 2018-01-22Bibliographically approved

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Dahlstrand, Hanna

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