A census of amplified and overexpressed human cancer genes

Key Points

  • Integrated screens of DNA copy number and gene expression in human cancers using microarray platforms have accelerated the rate of discovery of amplified and overexpressed genes. However, the biological importance of most of the genes identified in such studies remains unclear.

  • Amplification events often include multiple genes, so consideration of the pattern of genetic alteration alone is usually insufficient to identify which gene in an amplicon is being selected for owing to its contribution to oncogenesis. Supplementary datasets are usually required, including physical mapping, determination of overexpression, correlation with clinical outcome, biological investigations of function and, in some cases, efficacy of drugs targeted against the encoded overexpressed proteins.

  • In this Analysis we propose a weight-of-evidence based classification system for identifying individual genes in amplified regions that are selected for in an amplicon and so contribute to cancer development. The proposed classification scheme takes into account the complex and sometimes distinct datasets that are available for different amplicons in cancer.

  • Using this classification scheme in a census of the published literature, we have identified 77 genes for which there is evidence of involvement in human cancer development.

  • The 77 genes were divided into three classes based on the weight of supporting evidence. We consider that for class II (12 genes), and class I (3 genes) the evidence is sufficiently strong for their inclusion in the census of human cancer genes.

  • Linking newly generated integrated datasets to supporting evidence using the criteria outlined in this Analysis will aid in the future identification of amplified and overexpressed genes that contribute to cancer development.

Abstract

Integrated genome-wide screens of DNA copy number and gene expression in human cancers have accelerated the rate of discovery of amplified and overexpressed genes. However, the biological importance of most of the genes identified in such studies remains unclear. In this Analysis, we propose a weight-of-evidence based classification system for identifying individual genes in amplified regions that are selected for during tumour development. In a census of the published literature we have identified 77 genes for which there is good evidence of involvement in the development of human cancer.

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Figure 1: Idiogram.

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Acknowledgements

The authors thank the National Cancer Research Institute, the Grand Charity of Freemasons, the Prostate Cancer Charity, the Bob Champion Cancer Trust, the Prostate Cancer Research Foundation, and the Wellcome Trust for Support.

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Correspondence to Colin S. Cooper.

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The authors declare no competing financial interests.

Supplementary information

Supplementary information S1 (text)

A survey of amplified and overexpressed genes in human cancer (PDF 2900 kb)

Supplementary information S2 (table)

Amplified and overexpressed genes in human cancer (XLS 48 kb)

Supplementary information S3 (text)

A Review of Integrated datasets (PDF 342 kb)

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FURTHER INFORMATION

Cancer Genetics Programme at the sanger Centre

Institute for Cancer Research Amplified and Overexpressed Genes in Cancer (AOGIC) dataset

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Santarius, T., Shipley, J., Brewer, D. et al. A census of amplified and overexpressed human cancer genes. Nat Rev Cancer 10, 59–64 (2010). https://doi.org/10.1038/nrc2771

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