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Tissue, cell and stage specificity of (epi)mutations in cancers

Nature Reviews Cancer volume 5, pages 649–655 (2005)Cite this article

Abstract

Most (epi)mutations in cancers are specific to particular tumours or occur at specific stages of development, cell differentiation or tumorigenesis. Simple molecular mechanisms, such as tissue-restricted gene expression, seem to explain these associations only in rare cases. Instead, the specificity of (epi)mutations is probably due to the selection of a restricted spectrum of genetic changes by the cellular environment. In some cases, the resulting functional defects might be constrained to be neither too strong nor too weak for tumour growth to occur; that is, they lie within a 'window' that is permissive for tumorigenesis.

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Figure 1: Distribution of activating KRAS2 mutations in different tumour types.
Figure 2: PU.1 expression and acute myeloid leukaemia — a permissive 'window' for tumorigenesis.

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Acknowledgements

We are grateful to Richard Poulsom and Richard Houlston for critical comments on this manuscript, and to Gavin Kelly for assistance with the statistical analyses.

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Authors and Affiliations

  1. Molecular and Population Genetics Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln's Inn Fields, London, WC2A 3PX, UK

    Oliver M. Sieber & Ian P. M. Tomlinson

  2. Computational Genome Analysis Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln's Inn Fields, London, WC2A 3PX, UK

    Simon R. Tomlinson

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  1. Oliver M. Sieber
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DATABASES

Entrez Gene

APC

BRCA1

BRCA2

KRAS

MXI1

MYH

Sfpi1

TP53

National Cancer institute

breast cancer

colorectal cancer

acute myeloid

leukaemia

lymphoma

pancreatic cancer

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Sieber, O., Tomlinson, S. & Tomlinson, I. Tissue, cell and stage specificity of (epi)mutations in cancers. Nat Rev Cancer 5, 649–655 (2005). https://doi.org/10.1038/nrc1674

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