Spatial niche formation but not malignant progression is a driving force for intratumoural heterogeneity
| Autor: | Carsten Grüllich, Wilfried Roth, Niels Grabe, Yanis Tolstov, Gita Schönberg, Luisa Hofer, Matthias Schlesner, Gregor Warsow, Gencay Hatiboglu, Joanne Nyarangi-Dix, Markus Hohenfellner, Dogu Teber, Boris Hadaschik, Britta Walter, Anette Duensing, Sanjay Isaac, Nina Korzeniewski, Sascha Pahernik, Dirk Jäger, Rouven Hoefflin, Xin Chen, Roland Eils, Stephan Macher-Goeppinger, Bernd Lahrmann, Holger Sültmann, Sven Perner, Daniel Hübschmann, Stefan Duensing, Cathleen Spath |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Science General Physics and Astronomy Biology medicine.disease_cause Article General Biochemistry Genetics and Molecular Biology Genetic Heterogeneity 03 medical and health sciences Cell Line Tumor Exome Sequencing Biomarkers Tumor Tumor Microenvironment Carcinoma medicine Humans ddc:610 Stage (cooking) Carcinoma Renal Cell Exome sequencing Neoplasm Staging Tumor microenvironment Mutation Multidisciplinary Genetic heterogeneity General Chemistry Prognosis medicine.disease Phenotype Kidney Neoplasms Clear cell renal cell carcinoma 030104 developmental biology Immunology Cancer research Signal Transduction |
| Zdroj: | Nature Communications Nature Communications, Vol 7, Iss 1, Pp 1-12 (2016) |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/ncomms11845 |
| Popis: | 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. It has been increasingly recognised that tumours are not made up of a homogeneous population of cells. Here, the authors show heterogeneous expression of five protein markers in renal cell cancer and demonstrate that the progression of the tumour does not influence the degree of heterogeneity in the tumour. |
| Databáze: | OpenAIRE |
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