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Spatial niche formation but not malignant progression is a driving force for intratumoural heterogeneity

Intratumoural heterogeneity (ITH) is a major cause of cancer-associated lethality. Extensive genomic ITH has previously been reported in clear cell renal cell carcinoma (ccRCC). Here we address the question whether ITH increases with malignant progression and can hence be exploited as a prognostic m...

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Main Authors: Höfflin, Rouven (Author) , Lahrmann, Bernd (Author) , Warsow, Gregor (Author) , Hübschmann, Daniel (Author) , Spath, Cathleen (Author) , Walter, Britta (Author) , Chen, Xin (Author) , Hofer, Luisa (Author) , Macher-Göppinger, Stephan (Author) , Tolstov, Yanis (Author) , Korzeniewski, Nina (Author) , Duensing, Anette (Author) , Grüllich, Carsten (Author) , Jäger, Dirk (Author) , Perner, Sven Roger (Author) , Schoenberg, Gita (Author) , Nyarangi-Dix, Joanne (Author) , Isaac, Sanjay (Author) , Hatiboglu, Gencay (Author) , Teber, Dogu (Author) , Hadaschik, Boris (Author) , Pahernik, Sascha (Author) , Roth, Wilfried (Author) , Eils, Roland (Author) , Schlesner, Matthias (Author) , Sültmann, Holger (Author) , Hohenfellner, Markus (Author) , Grabe, Niels (Author) , Duensing, Stefan (Author)
Format: Article (Journal)
Language:English
Published: 13 Jun 2016
In: Nature Communications
Year: 2016, Volume: 7
ISSN:2041-1723
DOI:10.1038/ncomms11845
Online Access:Verlag, Volltext: https://doi.org/10.1038/ncomms11845
Verlag, Volltext: https://www.nature.com/articles/ncomms11845
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Author Notes:Rouven Hoefflin, Bernd Lahrmann, Gregor Warsow, Daniel Hübschmann, Cathleen Spath, Britta Walter, Xin Chen, Luisa Hofer, Stephan Macher-Goeppinger, Yanis Tolstov, Nina Korzeniewski, Anette Duensing, Carsten Grüllich, Dirk Jäger, Sven Perner, Gita Schönberg, Joanne Nyarangi-Dix, Sanjay Isaac, Gencay Hatiboglu, Dogu Teber, Boris Hadaschik, Sascha Pahernik, Wilfried Roth, Roland Eils, Matthias Schlesner, Holger Sültmann, Markus Hohenfellner, Niels Grabe and Stefan Duensing
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Summary:Intratumoural heterogeneity (ITH) is a major cause of cancer-associated lethality. Extensive genomic ITH has previously been reported in clear cell renal cell carcinoma (ccRCC). Here we address the question whether ITH increases with malignant progression and can hence be exploited as a prognostic marker. Unexpectedly, precision quantitative image analysis reveals that the degree of functional ITH is virtually identical between primary ccRCCs of the lowest stage and advanced, metastatic tumours. Functional ITH was found to show a stage-independent topological pattern with peak proliferative and signalling activities almost exclusively in the tumour periphery. Exome sequencing of matching peripheral and central primary tumour specimens reveals various region-specific mutations. However, these mutations cannot directly explain the zonal pattern suggesting a role of microenvironmental factors in shaping functional ITH. In conclusion, our results indicate that ITH is an early and general characteristic of malignant growth rather than a consequence of malignant progression.
Item Description:Gesehen am 15.04.2019
Physical Description:Online Resource
ISSN:2041-1723
DOI:10.1038/ncomms11845

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