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Rare ribosomopathies: insights into mechanisms of cancer

Nature Reviews Cancer volume 19, pages 228–238 (2019)Cite this article

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Abstract

Long thought to be too big and too ubiquitous to fail, we now know that human cells can fail to make sufficient amounts of ribosomes, causing a number of diseases collectively known as ribosomopathies. The best characterized ribosomopathies, with the exception of Treacher Collins syndrome, are inherited bone marrow failure syndromes, each of which has a marked increase in cancer predisposition relative to the general population. Although rare, emerging data reveal that the inherited bone marrow failure syndromes may be underdiagnosed on the basis of classical symptomology, leaving undiagnosed patients with these syndromes at an elevated risk of cancer without adequate counselling and surveillance. The link between the inherited ribosomopathies and cancer has led to greater awareness that somatic mutations in factors involved in ribosome biogenesis may also be drivers in sporadic cancers. Our goal here is to compare and contrast the pathophysiological mechanisms underpinning ribosomopathies to gain a better understanding of the mechanisms that predispose these disorders to cancer.

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Fig. 1: Ribosomopathies affect different steps of ribosome synthesis.
Fig. 2: Nucleolar stress response is induced by defective ribosome assembly.
Fig. 3: Translational alterations in ribosomopathies.
Fig. 4: Disruption of ribosome synthesis and function can promote tumorigenesis.

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Nature Reviews Cancer thanks D. Lafontaine, L. Montanaro and the other anonymous reviewer(s) for their contribution to the peer review of this work.

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  1. Department of Health Sciences, University of Piemonte Orientale, Novara, Italy

    Anna Aspesi

  2. Department of Biochemistry and Molecular Genetics, University of Louisville, Louisville, KY, USA

    Steven R. Ellis

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Glossary

2'-O-methylation

The addition, mostly found in pre-rRNA, of a methyl group at the 2' position of the ribose by ribonucleoprotein complexes containing C/D box family small nucleolar RNA.

Pseudouridylation

The isomerization of uridine due to a 180° rotation for which the uracil is attached to the ribose via a carbon–carbon instead of a nitrogen–carbon glycosidic bond.

Myelodysplastic syndrome

A heterogeneous group of clonal disorders characterized by ineffective haematopoiesis and cytopenias that may evolve into acute myeloid leukaemia.

Metaphyseal chondrodysplasia

A defective bone development causing short stature.

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Aspesi, A., Ellis, S.R. Rare ribosomopathies: insights into mechanisms of cancer. Nat Rev Cancer 19, 228–238 (2019). https://doi.org/10.1038/s41568-019-0105-0

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