High level of telomerase RNA gene expression is associated with chromatin modification, the ALT phenotype and poor prognosis in liposarcoma

Cairney, C., Hoare, S., Daidone, M., Zaffaroni, N. and Keith, W. (2008) High level of telomerase RNA gene expression is associated with chromatin modification, the ALT phenotype and poor prognosis in liposarcoma. British Journal of Cancer, 98(8), pp. 1467-1474. (doi:10.1038/sj.bjc.6604328)

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Abstract

Telomere length is maintained by two known mechanisms, activation of telomerase or alternative lengthening of telomeres (ALT). The ALT pathway is more commonly activated in tumours of mesenchymal origin, although the mechanisms involved in the decision of a cell to activate either telomerase or ALT are unknown at present and no molecular markers exist to define the ALT phenotype. We have previously shown an association between chromatin remodelling, telomerase gene expression and ALT in cell line models. Here, we evaluate these findings and investigate their prognostic significance in a panel of liposarcoma tissue samples to understand the biology underlying the ALT phenotype. Liposarcoma samples were split into three groups: telomerase positive (Tel+); ALT positive; ALT-/Tel- . Differences in telomerase gene expression were evident between the groups with increased expression of hTR in ALT and Tel+ compared to ALT-/Tel- samples and increased hTERT in Tel+ samples only. Investigation of a small panel of chromatin modifications revealed significantly increased binding of acetyl H3 in association with hTR expression. We confirm that the presence of the ALT phenotype is associated with poor prognosis and in addition, for the first time, we show a direct association between hTR expression and poor prognosis in liposarcoma patients.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Hoare, Miss Stacey and Cairney, Dr Claire and Keith, Professor Nicol
Authors: Cairney, C., Hoare, S., Daidone, M., Zaffaroni, N., and Keith, W.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:British Journal of Cancer
Journal Abbr.:Brit J Cancer
ISSN:0007-0920
ISSN (Online):1532-1827
Published Online:15 April 2008

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