Human Molecular Genetics Advance Access published online on May 12, 2006
Human Molecular Genetics, doi:10.1093/hmg/ddl128
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1 University of Liverpool Cancer Research Centre, Roy Castle Lung Cancer Research Programme, 200 London Road, Liverpool L3 9TA, UK
* To whom correspondence should be addressed. Lung cancer demonstrates the highest mortality in the UK. Previous studies have implicated allelic loss at chromosome 17q in the development of non-small cell lung carcinoma (NSCLC), and a number of known and putative tumour-suppressor genes reside within this region. One candidate tumour-suppressor gene is cytoglobin (CYGB), which is contained entirely within the 42.5kb Tylosis with Oesophageal Cancer (TOC) minimal region. CYGB abnormalities have only been demonstrated in sporadic head & neck cancers. In this study, we investigated the expression, promoter methylation and allelic imbalance status of this gene in 52 paired (normal / tumour) surgically excised lung tissue samples from patients with NSCLC. CYGB expression in tumour tissue was significantly reduced compared to corresponding adjacent normal in 54% of the examined cases (paired T-test, p < 0.001). The CYGB promoter was shown by pyrosequencing to be significantly hypermethylated (2-fold increase of methylation index in tumours) in 25/52 (48%) tumour compared to normal samples. The methylation index (MtI) of the CYGB promoter was associated with CYGB mRNA expression (linear regression analysis, p = 0.009) suggesting a primary role for the epigenetic events in CYGB silencing. In addition frequent LOH was detected at the locus 17q25 in 32/48 (67%) tumours examined. It is of note that the loss of expression intensified when both LOH and hypermethylation coincided in samples (Mann-Whitney, p = 0.049).The above findings provide the first evidence to suggest the implication of CYGB in the pathogenesis of NSCLCs.
Received March 9, 2006
Revised May 10, 2006
Accepted May 10, 2006
Article
Frequent genetic and epigenetic abnormalities contribute to the deregulation of Cytoglobin in non-small cell lung cancer
George Xinarianos 1,
Fiona E. McRonald 2,
Janet M. Risk 2,
Naomi L Bowers 1,
Georgios Nikolaidis 1,
John K. Field 3,
and
Triantafillos Liloglou 1 *
2 Molecular Genetics & Oncology Group, School of Clinical Dental Sciences, University of Liverpool, Liverpool L69 3BX, UK
3 University of Liverpool Cancer Research Centre, Roy Castle Lung Cancer Research Programme, 200 London Road, Liverpool L3 9TA, UK; Molecular Genetics & Oncology Group, School of Clinical Dental Sciences, University of Liverpool, Liverpool L69 3BX, UK
Triantafillos Liloglou, E-mail: liloglout{at}roycastle.liv.ac.uk
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