Chromosomal copy number heterogeneity predicts survival rates across cancers
Creators
- van Dijk, Erik1
- van den Bosch, Tom2
- Lenos, Kristiaan J2
- El Makrini, Khalid2
- Nijman, Lissanne E2
- Lansu, Nico3
- Boekhout, Michiel4
- Hageman, Joris H4
- Fitzgerald, Rebecca C5
- Punt, Cornelis J A6
- Tuynman, Jurriaan B7
- Snippert, Hugo J G4
- Kops, Geert J P L3
- Medema, Jan Paul2
- Ylstra, Bauke1
- Vermeulen, Louis8
- Miedema, Daniel M9
- 1. Department of Pathology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
- 2. LEXOR, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam and Amsterdam Gastroenterology & Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands., Oncode Institute, Amsterdam, The Netherlands.
- 3. Oncode Institute, Amsterdam, The Netherlands. Hubrecht institute-KNAW and University Medical Center Utrecht, Utrecht, The Netherlands
- 4. Oncode Institute, Amsterdam, The Netherlands. Center for Molecular Medicine, University Medical Centre Utrecht, Utrecht, The Netherlands.
- 5. MRC Cancer Unit, University of Cambridge, Cambridge, UK.
- 6. Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
- 7. Department of Surgery, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
- 8. LEXOR, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam and Amsterdam Gastroenterology & Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.Oncode Institute, Amsterdam, The Netherlands.
- 9. LEXOR, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam and Amsterdam Gastroenterology & Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. Oncode Institute, Amsterdam, The Netherlands
Description
Survival rates of cancer patients vary widely within and between malignancies. While genetic aberrations are at the root of all cancers, individual genomic features cannot explain these distinct disease outcomes. In contrast, intra-tumour heterogeneity (ITH) has the potential to elucidate pan-cancer survival rates and the biology that drives cancer prognosis. Unfortunately, a comprehensive and effective framework to measure ITH across cancers is missing. Here, we introduce a scalable measure of chromosomal copy number heterogeneity (CNH) that predicts patient survival across cancers. We show that the level of ITH can be derived from a single-sample copy number profile. Using gene-expression data and live cell imaging we demonstrate that ongoing chromosomal instability underlies the observed heterogeneity. Analysing 11,534 primary cancer samples from 37 different malignancies, we find that copy number heterogeneity can be accurately deduced and predicts cancer survival across tissues of origin and stages of disease. Our results provide a unifying molecular explanation for the different survival rates observed between cancer types.
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Additional details
Related works
- Cites
- Dataset: GSE36864 (geo)
- Dataset: https://ega-archive.org/studies/EGAS00001002617 (URL)
- Is published in
- Dataset: https://ega-archive.org/studies/EGAS00001004702 (URL)