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

K Lafferty-Whyte, C J Cairney, M B Will, N Serakinci, M-G Daidone, N Zaffaroni, A Bilsland, W N Keith

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Udgivelsesdato: 2009-Oct-29
OriginalsprogEngelsk
TidsskriftOncogene
Vol/bind28
Udgave nummer43
Sider (fra-til)3765-74
Antal sider9
ISSN0950-9232
DOI
StatusUdgivet - 29. okt. 2009

Fingeraftryk

Telomere Homeostasis
Telomerase
Mesenchymal Stromal Cells
Transcriptome
Liposarcoma
Cell Line
Chromatin Assembly and Disassembly
Telomere
Gene Expression Profiling
human TERT protein

Citer dette

Lafferty-Whyte, K., Cairney, C. J., Will, M. B., Serakinci, N., Daidone, M-G., Zaffaroni, N., ... 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), 3765-74. https://doi.org/10.1038/onc.2009.238
Lafferty-Whyte, K ; Cairney, C J ; Will, M B ; Serakinci, N ; Daidone, M-G ; Zaffaroni, N ; Bilsland, A ; Keith, W N. / A gene expression signature classifying telomerase and ALT immortalization reveals an hTERT regulatory network and suggests a mesenchymal stem cell origin for ALT. I: Oncogene. 2009 ; Bind 28, Nr. 43. s. 3765-74.
@article{40c5a9b0fc2c11deaefb000ea68e967b,
title = "A gene expression signature classifying telomerase and ALT immortalization reveals an hTERT regulatory network and suggests a mesenchymal stem cell origin for ALT",
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.",
keywords = "Cell Line, Tumor, Gene Expression Profiling, Humans, Liposarcoma, Mesenchymal Stem Cells, Proto-Oncogene Proteins c-myc, Telomerase, Telomere",
author = "K Lafferty-Whyte and Cairney, {C J} and Will, {M B} and N Serakinci and M-G Daidone and N Zaffaroni and A Bilsland and Keith, {W N}",
year = "2009",
month = "10",
day = "29",
doi = "10.1038/onc.2009.238",
language = "English",
volume = "28",
pages = "3765--74",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",
number = "43",

}

Lafferty-Whyte, K, Cairney, CJ, Will, MB, Serakinci, N, Daidone, M-G, Zaffaroni, N, Bilsland, A & Keith, WN 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, bind 28, nr. 43, s. 3765-74. https://doi.org/10.1038/onc.2009.238

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; Keith, W N.

I: Oncogene, Bind 28, Nr. 43, 29.10.2009, s. 3765-74.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - A gene expression signature classifying telomerase and ALT immortalization reveals an hTERT regulatory network and suggests a mesenchymal stem cell origin for ALT

AU - Lafferty-Whyte, K

AU - Cairney, C J

AU - Will, M B

AU - Serakinci, N

AU - Daidone, M-G

AU - Zaffaroni, N

AU - Bilsland, A

AU - Keith, W N

PY - 2009/10/29

Y1 - 2009/10/29

N2 - 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.

AB - 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.

KW - Cell Line, Tumor

KW - Gene Expression Profiling

KW - Humans

KW - Liposarcoma

KW - Mesenchymal Stem Cells

KW - Proto-Oncogene Proteins c-myc

KW - Telomerase

KW - Telomere

U2 - 10.1038/onc.2009.238

DO - 10.1038/onc.2009.238

M3 - Journal article

C2 - 19684619

VL - 28

SP - 3765

EP - 3774

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 43

ER -