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Isolation and functional assessment of common, polymorphic variants of the B-MYB proto-oncogene associated with a reduced cancer risk

Oncogene volume 27, pages 2929–2933 (2008)Cite this article

A Corrigendum to this article was published on 22 May 2008

Abstract

The B-MYB proto-oncogene is a transcription factor belonging to the MYB family that is frequently overexpressed or amplified in different types of human malignancies. While it is suspected that B-MYB plays a role in human cancer, there is still no direct evidence of its causative role. Looking for mutations of the B-MYB gene in human cell lines and primary cancer samples, we frequently isolated two nonsynonymous B-MYB polymorphic variants (rs2070235 and rs11556379). Compared to the wild-type protein, the B-MYB isoforms display altered conformation, impaired regulation of target genes and decreased antiapoptotic activity, suggesting that they are hypomorphic variants of the major allele. Importantly, the B-MYB polymorphisms are common; rs2070235 and rs11556379 are found, depending on the ethnic background, in 10–50% of human subjects. We postulated that, if B-MYB activity is important for transformation, the presence of common, hypomorphic variants might modify cancer risk. Indeed, the B-MYB polymorphisms are underrepresented in 419 cancer patients compared to 230 controls (odds ratio 0.53; (95%) confidence interval 0.385–0.755; P=0.001). This data imply that a large fraction of the human population is carrier of B-MYB alleles that might be associated with a reduced risk of developing neoplastic disease.

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Acknowledgements

We thank Gianluca Sala, John Anderson, Pete Scambler and Nazneen Rahman for critical reading of the manuscript. This study was supported by the Neuroblastoma Society UK and SPARKS (to AS), the Italian Neuroblastoma Foundation (to GT), the Fondazione Cassa di Risparmio di Modena (to BC), the Ministry of University and Research (MIUR, Rome, Italy) Programma Triennale di Ricerca (Decreto no. 1588 to LI).

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Author notes

  1. R Schwab and R Bussolari: These authors contributed equally to this work.

Authors and Affiliations

  1. Molecular Haematology and Cancer Biology Unit, UCL Institute of Child Health, London, UK

    R Schwab, D Corvetta, O Chayka, G Santilli, J M-M Kwok, M Hubank & A Sala

  2. Department of Biomedical Sciences, Universita di Modena e Reggio Emilia, Modena, Italy

    R Bussolari, G F Amorotti & B Calabretta

  3. Dipartimento di Medicina Sperimentale Sezione di Biochimica, Biochimica Clinica e Biochimica dell'Esercizio Fisico Università degli Studi di Parma, Parma, Italy

    D Corvetta

  4. Translational Paediatric Oncology, National Institute for Cancer Research (IST), Genoa, Italy

    G P Tonini

  5. Laboratory of Genetic and Environmental Epidemiology, John Paul II Center for High Technology Research and Education in Biomedical Sciences, Catholic University, Campobasso, Italy

    L Iacoviello

  6. Immunologia e Diagnostica Molecolare Oncologica, Istituto Oncologico Veneto (IOV), IRCCS, Padova, Italy

    R Bertorelle & C Menin

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  1. R Schwab
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Corresponding author

Correspondence to A Sala.

Additional information

Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Schwab, R., Bussolari, R., Corvetta, D. et al. Isolation and functional assessment of common, polymorphic variants of the B-MYB proto-oncogene associated with a reduced cancer risk. Oncogene 27, 2929–2933 (2008). https://doi.org/10.1038/sj.onc.1210947

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