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  • Opinion
  • Published:

Tumorigenesis in Down's syndrome: big lessons from a small chromosome

Abstract

If assessed by a number of criteria for cancer predisposition, Down's syndrome (DS) should be an overwhelmingly cancer-prone condition. Although childhood leukaemias occur more frequently in DS, paradoxically, individuals with DS have a markedly lower incidence of most solid tumours. Understanding the mechanisms that are capable of overcoming such odds could potentially open new routes for cancer prevention and therapy. In this Opinion article, we discuss recent reports that suggest unique and only partially understood mechanisms behind this paradox, including tumour repression, anti-angiogenic effects and stem cell ageing and availability.

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Figure 1: Genes on Homo sapiens chromosome 21 that have direct roles in DS-associated cancer.
Figure 2: Anti-angiogenic effects of genes in trisomy 21.
Figure 3: Stem cell fate and ageing abnormalities in DS that might affect tumorigenesis.
Figure 4: Exhaustion-threshold model for the transformation fitness of ageing DS stem cells.

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Acknowledgements

The authors thank the AnEUploidy-Consortium EU-FP6, the Leukaemia and Lymphoma Research UK, Barts and The London Charity, British Society of Haematology, the Jerome Lejeune Foundation, the Kay Kendall Leukaemia Fund, and the LonDownS Consortium strategic funding award from The Wellcome Trust for funding their recent and current work.

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Nižetić, D., Groet, J. Tumorigenesis in Down's syndrome: big lessons from a small chromosome. Nat Rev Cancer 12, 721–732 (2012). https://doi.org/10.1038/nrc3355

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