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  • Oncogenomics
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Epigenetic inactivation of the candidate 3p21.3 suppressor gene BLU in human cancers

Oncogene volume 22, pages 1580–1588 (2003)Cite this article

Abstract

Many distinct regions of 3p show frequent allelic losses in a wide range of tumour types. Previously, the BLU candidate tumour suppressor gene (TSG) encoded by a gene-rich critical deleted region in 3p21.3 was found to be inactivated rarely in lung cancer, although expression was downregulated in a subset of lung tumour cell lines. To elucidate the role of BLU in tumorigenesis, we analysed BLU promoter methylation status in tumour cell lines and detected promoter region hypermethylation in 39% lung, 42% breast, 50% kidney, 86% neuroblastoma and 80% nasopharyngeal (NPC) tumour cell lines. Methylation of the BLU promoter region correlated with the downregulation of BLU transcript expression in tumour cell lines. Expression was recovered in tumour cell lines treated with 5-aza 2-deoxycytidine. Exogenous expression of BLU in neuroblastoma (SK-N-SH) and NSCLC (NCI-H1299) resulted in reduced colony formation efficiency, in vitro. Furthermore, methylation of the BLU promoter region was detected in primary sporadic SCLC (14%), NSCLC (19%) and neuroblastoma (41%). As frequent methylation of the RASSF1A 3p21.3 TSG has also been reported in these tumour types, we investigated whether BLU and RASSF1A methylation were independent or related events. No correlation was found between hypermethylation of RASSF1A and BLU promoter region CpG islands in SCLC or neuroblastoma. However, there was association between RASSF1A and BLU methylation in NSCLC (P=0.0031). Our data suggest that in SCLC and neuroblastoma, RASSF1A and BLU methylations are unrelated events and not a manifestation of a regional alteration in epigenetic status, while in NSCLC there may be a regional methylation effect. Together, these data suggest a significant role for epigenetic inactivation of BLU in the pathogenesis of common human cancers and that methylation inactivation of BLU occurs independent of RASSF1A in SCLC and neuroblastoma tumours.

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Acknowledgements

This work is supported in part by SPARKS (Sports Aiding Medical Research for Kids), Association for International Cancer Research, Cancer Research UK. SH is supported by the Portuguese Foundation for Science and Technology. TM is supported by the Swedish Cancer Society and the Swedish Children's Cancer Foundation. JDM supported by Grants NCI P50 CA70907 and CA71618.

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Author notes

  1. Sabine Zöchbauer-Müller

    Present address: Department of Medicine, Clinical Division of Oncology, University Hospital, Vienna, Austria

Authors and Affiliations

  1. Department of Paediatrics and Child Health, Section of Medical and Molecular Genetics, University of Birmingham, The Medical School, Edgbaston, Birmingham, B15 2TT, UK

    Angelo Agathanggelou, Ashraf Dallol, Sofia Honorio, Luke Hesson, Eamonn R Maher & Farida Latif

  2. Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Sabine Zöchbauer-Müller, Catherine Morrissey & John D Minna

  3. Department of Clinical Genetics, Gothenburg University, Sahlgrenska University, Hospital/Ostra, Gothenburg, S-416 85, Sweden

    Tommy Martinsson

  4. The Prince Charles Hospital, Rode Road, Chermside, Brisbane, 4032, Australia

    Kwun M Fong

  5. Birmingham Children's Hospital, Steelhouse Lane, Birmingham, B4 6NH, UK

    Michael J Kuo

  6. Department of Surgery, University of Hong Kong, Hong Kong, China

    Po Wing Yuen

  7. Cancer Research UK Renal Molecular Oncology Research Group, University of Birmingham, The Medical School, Birmingham, B15 2TT, UK

    Eamonn R Maher & Farida Latif

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  1. Angelo Agathanggelou
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Correspondence to Farida Latif.

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Agathanggelou, A., Dallol, A., Zöchbauer-Müller, S. et al. Epigenetic inactivation of the candidate 3p21.3 suppressor gene BLU in human cancers. Oncogene 22, 1580–1588 (2003). https://doi.org/10.1038/sj.onc.1206243

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