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

Angelo Agathanggelou, Ashraf Dallol, Sabine Zöchbauer-Müller, Catherine Morrissey, Sofia Honorio, Luke Hesson, Tommy Martinsson, Kwun M. Fong, Michael J. Kuo, Po Wing Yuen, Eamonn R. Maher, John D. Minna, Farida Latif

Research output: Contribution to journalArticle

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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 down-regulation 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.

Original languageEnglish (US)
Pages (from-to)1580-1588
Number of pages9
JournalOncogene
Volume22
Issue number10
DOIs
StatePublished - Mar 13 2003

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Suppressor Genes
Epigenomics
Methylation
Neuroblastoma
Tumor Cell Line
Genetic Promoter Regions
Neoplasms
decitabine
Tumor Suppressor Genes
Down-Regulation
Lung
CpG Islands
Loss of Heterozygosity
Lung Neoplasms
Carcinogenesis
Breast
Kidney

Keywords

  • 3p21.3 region
  • Epigenetic inactivation
  • Human cancers

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Agathanggelou, A., Dallol, A., Zöchbauer-Müller, S., Morrissey, C., Honorio, S., Hesson, L., ... Latif, F. (2003). Epigenetic inactivation of the candidate 3p21.3 suppressor gene BLU in human cancers. Oncogene, 22(10), 1580-1588. https://doi.org/10.1038/sj.onc.1206243

Epigenetic inactivation of the candidate 3p21.3 suppressor gene BLU in human cancers. / Agathanggelou, Angelo; Dallol, Ashraf; Zöchbauer-Müller, Sabine; Morrissey, Catherine; Honorio, Sofia; Hesson, Luke; Martinsson, Tommy; Fong, Kwun M.; Kuo, Michael J.; Yuen, Po Wing; Maher, Eamonn R.; Minna, John D.; Latif, Farida.

In: Oncogene, Vol. 22, No. 10, 13.03.2003, p. 1580-1588.

Research output: Contribution to journalArticle

Agathanggelou, A, Dallol, A, Zöchbauer-Müller, S, Morrissey, C, Honorio, S, Hesson, L, Martinsson, T, Fong, KM, Kuo, MJ, Yuen, PW, Maher, ER, Minna, JD & Latif, F 2003, 'Epigenetic inactivation of the candidate 3p21.3 suppressor gene BLU in human cancers', Oncogene, vol. 22, no. 10, pp. 1580-1588. https://doi.org/10.1038/sj.onc.1206243
Agathanggelou A, Dallol A, Zöchbauer-Müller S, Morrissey C, Honorio S, Hesson L et al. Epigenetic inactivation of the candidate 3p21.3 suppressor gene BLU in human cancers. Oncogene. 2003 Mar 13;22(10):1580-1588. https://doi.org/10.1038/sj.onc.1206243
Agathanggelou, Angelo ; Dallol, Ashraf ; Zöchbauer-Müller, Sabine ; Morrissey, Catherine ; Honorio, Sofia ; Hesson, Luke ; Martinsson, Tommy ; Fong, Kwun M. ; Kuo, Michael J. ; Yuen, Po Wing ; Maher, Eamonn R. ; Minna, John D. ; Latif, Farida. / Epigenetic inactivation of the candidate 3p21.3 suppressor gene BLU in human cancers. In: Oncogene. 2003 ; Vol. 22, No. 10. pp. 1580-1588.
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