Ontogenic growth as the root of fundamental differences between childhood and adult cancer

Benjamin Werner, Arne Traulsen, David Dingli

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Cancer, the unregulated proliferation of cells, can occur at any age and may arise from almost all cell types. However, the incidence and types of cancer differ with age. Some cancers are predominantly observed in children, others are mostly restricted to older ages. Treatment strategies of some cancers are very successful and cure is common in childhood, while treatment of the same cancer type is much more challenging in adults. Here, we develop a stochastic model of stem cell proliferation that considers both tissue development and homeostasis and discuss the disturbance of such a system by mutations. Due to changes in population size, mutant fitness becomes context dependent and consequently the effects of mutations on the stem cell population can vary with age. We discuss different mutant phenotypes and show the age dependency of their expected abundances. Most importantly, fitness of particular mutations can change with age and advantageous mutations can become deleterious or vice versa. This perspective can explain unique properties of childhood disorders, for example, the frequently observed phenomenon of a self-limiting leukemia in newborns with trisomy 21, but also explains other puzzling observations such as the increased risk of leukemia in patients with bone marrow failure or chemotherapy induced myelodysplasia.

Original languageEnglish (US)
Pages (from-to)543-550
Number of pages8
JournalStem Cells
Volume34
Issue number3
DOIs
StatePublished - Mar 1 2016

Keywords

  • Acute lymphocytic leukemia
  • Acute myelogenous leukemia
  • Adult haematopoietic stem cells
  • Cancer stem cells
  • Hemopoietic stem cells
  • Self-renewal

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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