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

Nat Rev Cancer. 2012 Oct;12(10):721-32. doi: 10.1038/nrc3355. Epub 2012 Sep 21.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / genetics
  • Cell Transformation, Neoplastic*
  • Cellular Senescence
  • Chromosomal Instability
  • Chromosomes, Human, Pair 21 / genetics*
  • Down Syndrome / complications
  • Down Syndrome / genetics*
  • Down Syndrome / immunology
  • Genes, Tumor Suppressor
  • Genetic Predisposition to Disease
  • Humans
  • Neoplasms / blood supply
  • Neoplasms / epidemiology*
  • Neoplasms / genetics*
  • Neovascularization, Pathologic
  • Oncogenes
  • Stem Cells / physiology