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

Nobuyuki Tanaka, Shigeaki Kanatani, Raju Tomer, Cecilia Sahlgren, Pauliina Kronqvist, Dagmara Kaczynska, Lauri Louhivuori, Lorand Kis, Claes Lindh, Przemysław Mitura, Andrzej Stepulak, Sara Corvigno, Johan Hartman, Patrick Micke, Artur Mezheyeuski, Carina Strell, Joseph W. Carlson, Carlos Fernández Moro, Hanna Dahlstrand, Arne ÖstmanKazuhiro Matsumoto, Peter Wiklund, Mototsugu Oya, Ayako Miyakawa, Karl Deisseroth, Per Uhlén

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51 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)796-806
Number of pages11
JournalNature Biomedical Engineering
Volume1
Issue number10
DOIs
Publication statusPublished - 1 Oct 2017

Cite this

Tanaka, 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, J. W., Fernández Moro, C., Dahlstrand, H., ... Uhlén, P. (2017). Whole-tissue biopsy phenotyping of three-dimensional tumours reveals patterns of cancer heterogeneity. Nature Biomedical Engineering, 1(10), 796-806. https://doi.org/10.1038/s41551-017-0139-0