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Whole-tissue biopsy phenotyping of three-dimensional tumours reveals patterns of cancer heterogeneity




TekijätTanaka N, Kanatani S, Tomer R, Sahlgren C, Kronqvist P, Kaczynska D, Louhivuori L, Kis L, Lindh C, Mitura P, Stepulak A, Corvigno S, Hartman J, Micke P, Mezheyeuski A, Strell C, Carlson JW, Moro CF, Dahlstrand H, Ostman A, Matsumoto K, Wiklund P, Oya M, Miyakawa A, Deisseroth K, Uhlen P

KustantajaNATURE PUBLISHING GROUP

Julkaisuvuosi2017

JournalNature Biomedical Engineering

Tietokannassa oleva lehden nimiNATURE BIOMEDICAL ENGINEERING

Lehden akronyymiNAT BIOMED ENG

Vuosikerta1

Numero10

Aloitussivu796

Lopetussivu806

Sivujen määrä11

ISSN2157-846X

DOIhttps://doi.org/10.1038/s41551-017-0139-0


Tiivistelmä
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.



Last updated on 2024-26-11 at 10:39