A gene expression signature classifying telomerase and ALT immortalization reveals an hTERT regulatory network and suggests a mesenchymal stem cell origin for ALT

Lafferty-Whyte, K., Cairney, C.J., Will, M.B., Serakinci, N., Daidone, M.G., Zaffaroni, N., Bilsland, A.E. and Keith, W.N. (2009) A gene expression signature classifying telomerase and ALT immortalization reveals an hTERT regulatory network and suggests a mesenchymal stem cell origin for ALT. Oncogene, 28(43), pp. 3765-3774. (doi:10.1038/onc.2009.238)

Full text not currently available from Enlighten.

Abstract

Telomere length is maintained by two known mechanisms, the activation of telomerase or alternative lengthening of telomeres (ALT). The molecular mechanisms regulating the ALT phenotype are poorly understood and it is unknown how the decision of which pathway to activate is made at the cellular level. We have shown earlier that active repression of telomerase gene expression by chromatin remodelling of the promoters is one mechanism of regulation; however, other genes and signalling networks are likely to be required to regulate telomerase and maintain the ALT phenotype. Using gene expression profiling, we have uncovered a signature of 1305 genes to distinguish telomerase-positive and ALT cell lines. By combining this with the gene expression profiles of liposarcoma tissue samples, we refined this signature to 297 genes. A network analysis of known interactions between genes within this signature revealed a regulatory signalling network consistent with a model of human telomerase reverse transcriptase (hTERT) repression in ALT cell lines and liposarcomas. This network expands on our existing knowledge of hTERT regulation and provides a platform to understand differential regulation of hTERT in different tumour types and normal tissues. We also show evidence to suggest a novel mesenchymal stem cell origin for ALT immortalization in cell lines and mesenchymal tissues.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Bilsland, Dr Alan and Cairney, Dr Claire and Keith, Professor Nicol
Authors: Lafferty-Whyte, K., Cairney, C.J., Will, M.B., Serakinci, N., Daidone, M.G., Zaffaroni, N., Bilsland, A.E., and Keith, W.N.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Oncogene
ISSN:0950-9232
ISSN (Online):1476-5594
Published Online:17 August 2009

University Staff: Request a correction | Enlighten Editors: Update this record