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The prenatal origins of cancer

Abstract

The concept that some childhood malignancies arise from postnatally persistent embryonal cells has a long history. Recent research has strengthened the links between driver mutations and embryonal and early postnatal development. This evidence, coupled with much greater detail on the cell of origin and the initial steps in embryonal cancer initiation, has identified important therapeutic targets and provided renewed interest in strategies for the early detection and prevention of childhood cancer.

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Figure 1: Neural crest development and neuroblastoma.
Figure 2: TMD and ML–DS.
Figure 3: The development of B-ALL.
Figure 4: Cerebellar development and embryonal origin of medulloblastoma.
Figure 5: A model of embryonal tumorigenesis.

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Acknowledgements

G.M.M., B.B.C., D.R.C. and T.L. are supported by grants from the Australian National Health and Medical Research Council (NHMRC), the Cancer Institute New South Wales, Australia, the Cancer Council New South Wales, Australia, and the Steven Walter Children's Cancer Foundation. T.L. is an Australian Research Council (ARC) Research Fellow. M.K.M. is supported by a fellowship from the Kids Cancer Project. J.G.M. and W.A.W. are supported by US National Institutes of Health (NIH) grants F30CA174154, U01CA176287, R01CA133091, R01CA102321, R01CA148699, R01CA159859, U54CA163155 and P01CA081403, as well as the Katie Dougherty, Pediatric Brain Tumor and Samuel G. Waxman Foundations. Sydney Children's Hospital, Randwick, New South Wales, Australia, and the Children's Cancer Institute Australia for Medical Research, Randwick, New South Wales, Australia, are affiliated with the University of New South Wales, Sydney, Australia. The authors apologize to the numerous colleagues whose important contributions could not be included in this Opinion article owing to space limitations.

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Glossary

Adaptive B2 cells

B2 cells that are responsible for the production of antibodies during adaptive immunity.

Anlage

The initial clustering of embryonic cells from which an organ or part of an organ will form.

Chromothripsis

A process whereby a single catastrophic event within the genome leads to multiple genetic alterations across one or more chromosomes.

Innate B1 precursor cells

B1 cells with innate sensing and responding properties.

Marginal zone B cells

B cells from the marginal zone of the spleen, which is a unique lymphoid area located at the interface between the circulation and the immune system.

Neonatal blood spot

A card with a drop of blood collected from the heel of a newborn baby. Neonatal blood spots are used to screen neonates for rare but serious metabolic conditions.

Neural crest

A transient collection of multipotent embryonic progenitors in the developing ectoderm that gives rise to a multitude of different cell types, including melanocytes, craniofacial chondrocytes and osteocytes, smooth muscle myocytes and peripheral nervous system neurons.

Rostrally

Pertaining to being situated towards the oral or nasal region, or in the case of the brain, towards the tip of the frontal lobe.

Somites

Bilaterally paired blocks of mesoderm that form along the anterior–posterior axis of the developing embryo.

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Marshall, G., Carter, D., Cheung, B. et al. The prenatal origins of cancer. Nat Rev Cancer 14, 277–289 (2014). https://doi.org/10.1038/nrc3679

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