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 language | English |
|---|---|
| Pages (from-to) | 796-806 |
| Number of pages | 11 |
| Journal | Nature Biomedical Engineering |
| Volume | 1 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - 2017 Oct 1 |
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ASJC Scopus subject areas
- Biotechnology
- Bioengineering
- Medicine (miscellaneous)
- Biomedical Engineering
- Computer Science Applications
Cite this
Whole-tissue biopsy phenotyping of three-dimensional tumours reveals patterns of cancer heterogeneity. / Tanaka, Nobuyuki; Kanatani, Shigeaki; Tomer, Raju; Sahlgren, Cecilia; Kronqvist, Pauliina; Kaczynska, Dagmara; Louhivuori, Lauri; Kis, Lorand; Lindh, Claes; Mitura, Przemysław; Stepulak, Andrzej; Corvigno, Sara; Hartman, Johan; Micke, Patrick; Mezheyeuski, Artur; Strell, Carina; Carlson, Joseph W.; Fernández Moro, Carlos; Dahlstrand, Hanna; Östman, Arne; Matsumoto, Kazuhiro; Wiklund, Peter; Oya, Mototsugu; Miyakawa, Ayako; Deisseroth, Karl; Uhlén, Per.
In: Nature Biomedical Engineering, Vol. 1, No. 10, 01.10.2017, p. 796-806.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Whole-tissue biopsy phenotyping of three-dimensional tumours reveals patterns of cancer heterogeneity
AU - Tanaka, Nobuyuki
AU - Kanatani, Shigeaki
AU - Tomer, Raju
AU - Sahlgren, Cecilia
AU - Kronqvist, Pauliina
AU - Kaczynska, Dagmara
AU - Louhivuori, Lauri
AU - Kis, Lorand
AU - Lindh, Claes
AU - Mitura, Przemysław
AU - Stepulak, Andrzej
AU - Corvigno, Sara
AU - Hartman, Johan
AU - Micke, Patrick
AU - Mezheyeuski, Artur
AU - Strell, Carina
AU - Carlson, Joseph W.
AU - Fernández Moro, Carlos
AU - Dahlstrand, Hanna
AU - Östman, Arne
AU - Matsumoto, Kazuhiro
AU - Wiklund, Peter
AU - Oya, Mototsugu
AU - Miyakawa, Ayako
AU - Deisseroth, Karl
AU - Uhlén, Per
PY - 2017/10/1
Y1 - 2017/10/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=85034610370&partnerID=8YFLogxK
U2 - 10.1038/s41551-017-0139-0
DO - 10.1038/s41551-017-0139-0
M3 - Article
VL - 1
SP - 796
EP - 806
JO - Nature Biomedical Engineering
JF - Nature Biomedical Engineering
SN - 2157-846X
IS - 10
ER -