Discovery - University of Dundee - Online Publications

Library & Learning Centre

NT5E (CD73) is epigenetically regulated in malignant melanoma and associated with metastatic site specificity

Standard

NT5E (CD73) is epigenetically regulated in malignant melanoma and associated with metastatic site specificity. / Wang, H.; Lee, S.; Lo Nigro, C.; Lattanzio, L.; Merlano, M.; Monteverde, M.; Matin, R.; Purdie, K.; Mladkova, N.; Bergamaschi, D.; Harwood, C.; Syed, N.; Szlosarek, P.; Briasoulis, E.; McHugh, A.; Thompson, A.; Evans, A.; Leigh, I.; Fleming, C.; Inman, G. J.; Hatzimichael, E; Proby, C.; Crook, Tim.

In: British Journal of Cancer, Vol. 106, No. 8, 2012, p. 1446-52.

Research output: Contribution to journalArticle

Harvard

Wang, H, Lee, S, Lo Nigro, C, Lattanzio, L, Merlano, M, Monteverde, M, Matin, R, Purdie, K, Mladkova, N, Bergamaschi, D, Harwood, C, Syed, N, Szlosarek, P, Briasoulis, E, McHugh, A, Thompson, A, Evans, A, Leigh, I, Fleming, C, Inman, GJ, Hatzimichael, E, Proby, C & Crook, T 2012, 'NT5E (CD73) is epigenetically regulated in malignant melanoma and associated with metastatic site specificity' British Journal of Cancer, vol 106, no. 8, pp. 1446-52.

APA

Wang, H., Lee, S., Lo Nigro, C., Lattanzio, L., Merlano, M., Monteverde, M., Matin, R., Purdie, K., Mladkova, N., Bergamaschi, D., Harwood, C., Syed, N., Szlosarek, P., Briasoulis, E., McHugh, A., Thompson, A., Evans, A., Leigh, I., Fleming, C., Inman, G. J., Hatzimichael, E., Proby, C., & Crook, T. (2012). NT5E (CD73) is epigenetically regulated in malignant melanoma and associated with metastatic site specificity. British Journal of Cancer, 106(8), 1446-52doi: 10.1038/bjc.2012.95

Vancouver

Wang H, Lee S, Lo Nigro C, Lattanzio L, Merlano M, Monteverde M et al. NT5E (CD73) is epigenetically regulated in malignant melanoma and associated with metastatic site specificity. British Journal of Cancer. 2012;106(8):1446-52.

Author

Wang, H.; Lee, S.; Lo Nigro, C.; Lattanzio, L.; Merlano, M.; Monteverde, M.; Matin, R.; Purdie, K.; Mladkova, N.; Bergamaschi, D.; Harwood, C.; Syed, N.; Szlosarek, P.; Briasoulis, E.; McHugh, A.; Thompson, A.; Evans, A.; Leigh, I.; Fleming, C.; Inman, G. J.; Hatzimichael, E; Proby, C.; Crook, Tim / NT5E (CD73) is epigenetically regulated in malignant melanoma and associated with metastatic site specificity.

In: British Journal of Cancer, Vol. 106, No. 8, 2012, p. 1446-52.

Research output: Contribution to journalArticle

Bibtex - Download

@article{872d426e51214d40b556d92876148f3e,
title = "NT5E (CD73) is epigenetically regulated in malignant melanoma and associated with metastatic site specificity",
author = "H. Wang and S. Lee and {Lo Nigro}, C. and L. Lattanzio and M. Merlano and M. Monteverde and R. Matin and K. Purdie and N. Mladkova and D. Bergamaschi and C. Harwood and N. Syed and P. Szlosarek and E. Briasoulis and A. McHugh and A. Thompson and A. Evans and I. Leigh and C. Fleming and Inman, {G. J.} and E Hatzimichael and C. Proby and Tim Crook",
year = "2012",
volume = "106",
number = "8",
pages = "1446--52",
journal = "British Journal of Cancer",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - NT5E (CD73) is epigenetically regulated in malignant melanoma and associated with metastatic site specificity

A1 - Wang,H.

A1 - Lee,S.

A1 - Lo Nigro,C.

A1 - Lattanzio,L.

A1 - Merlano,M.

A1 - Monteverde,M.

A1 - Matin,R.

A1 - Purdie,K.

A1 - Mladkova,N.

A1 - Bergamaschi,D.

A1 - Harwood,C.

A1 - Syed,N.

A1 - Szlosarek,P.

A1 - Briasoulis,E.

A1 - McHugh,A.

A1 - Thompson,A.

A1 - Evans,A.

A1 - Leigh,I.

A1 - Fleming,C.

A1 - Inman,G. J.

A1 - Hatzimichael,E

A1 - Proby,C.

A1 - Crook,Tim

AU - Wang,H.

AU - Lee,S.

AU - Lo Nigro,C.

AU - Lattanzio,L.

AU - Merlano,M.

AU - Monteverde,M.

AU - Matin,R.

AU - Purdie,K.

AU - Mladkova,N.

AU - Bergamaschi,D.

AU - Harwood,C.

AU - Syed,N.

AU - Szlosarek,P.

AU - Briasoulis,E.

AU - McHugh,A.

AU - Thompson,A.

AU - Evans,A.

AU - Leigh,I.

AU - Fleming,C.

AU - Inman,G. J.

AU - Hatzimichael,E

AU - Proby,C.

AU - Crook,Tim

PY - 2012

Y1 - 2012

N2 - Background:Novel prognostic biomarkers and therapeutic strategies are urgently required for malignant melanoma. Ecto-5-prime-nucleotidase (NT5E; CD73) overexpression has been reported in several human cancers. The mechanism(s) underlying deregulated expression and the clinical consequences of changes in expression are not known.Methods:We used RT-PCR, qPCR, methylation-specific PCR and pyrosequencing to analyse expression and regulation of NT5E in malignant melanoma cell lines and primary and metastatic melanomas.Results:NT5E is subject to epigenetic regulation in melanoma. NT5E mRNA is downregulated by methylation-dependent transcriptional silencing in the melanoma cell lines SKMel2, SKMel23, WM35, Mel501, Mel505 and C81-61 and expression is reactivated by azacytidine. In contrast, the CpG island is unmethylated and the gene expressed in cultured normal melanocytes. In clinical cases of melanoma, methylation in the NT5E CpG island occurs in both primary and metastatic melanomas and correlates with transcriptional downregulation of NT5E mRNA. Relapse with metastatic disease, particularly to the visceral sites and brain, is more common in primary melanomas lacking NT5E methylation. Primary melanomas with methylation in NT5E show limited metastatic potential or more commonly metastasise predominantly to nodal sites rather than viscera and brain (P=0.01).Conclusion:Deregulation of NT5E expression in melanoma occurs via epigenetic changes in the NT5E CpG island. Confirmation of our results in larger clinical series would support the candidacy of NT5E as a clinical biomarker in melanoma, which could be applied in both primary and relapsed disease. Inhibition of NT5E may have therapeutic potential in melanoma, particularly in patients with more aggressive disease metastatic to viscera or the brain.

AB - Background:Novel prognostic biomarkers and therapeutic strategies are urgently required for malignant melanoma. Ecto-5-prime-nucleotidase (NT5E; CD73) overexpression has been reported in several human cancers. The mechanism(s) underlying deregulated expression and the clinical consequences of changes in expression are not known.Methods:We used RT-PCR, qPCR, methylation-specific PCR and pyrosequencing to analyse expression and regulation of NT5E in malignant melanoma cell lines and primary and metastatic melanomas.Results:NT5E is subject to epigenetic regulation in melanoma. NT5E mRNA is downregulated by methylation-dependent transcriptional silencing in the melanoma cell lines SKMel2, SKMel23, WM35, Mel501, Mel505 and C81-61 and expression is reactivated by azacytidine. In contrast, the CpG island is unmethylated and the gene expressed in cultured normal melanocytes. In clinical cases of melanoma, methylation in the NT5E CpG island occurs in both primary and metastatic melanomas and correlates with transcriptional downregulation of NT5E mRNA. Relapse with metastatic disease, particularly to the visceral sites and brain, is more common in primary melanomas lacking NT5E methylation. Primary melanomas with methylation in NT5E show limited metastatic potential or more commonly metastasise predominantly to nodal sites rather than viscera and brain (P=0.01).Conclusion:Deregulation of NT5E expression in melanoma occurs via epigenetic changes in the NT5E CpG island. Confirmation of our results in larger clinical series would support the candidacy of NT5E as a clinical biomarker in melanoma, which could be applied in both primary and relapsed disease. Inhibition of NT5E may have therapeutic potential in melanoma, particularly in patients with more aggressive disease metastatic to viscera or the brain.

U2 - 10.1038/bjc.2012.95

DO - 10.1038/bjc.2012.95

M1 - Article

JO - British Journal of Cancer

JF - British Journal of Cancer

IS - 8

VL - 106

SP - 1446

EP - 1452

ER -

Documents

Library & Learning Centre

Contact | Accessibility | Policy