Expression profiles of Telomerase+ vs. ALT+ G3 Atm-/-TERT-ER T-cell lymphomas
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE35044 | GEO | 2012/01/17
SECONDARY ACCESSION(S): PRJNA155951
REPOSITORIES: GEO
Similar Datasets
Project description:We used microarray profiling to document the difference between telomerase+ vs. ALT+ T-cell lymphomas developed on G3 Atm-/-TERT-ER genetic background. T-cell lymphomas were developed in G3 Atm-/-TERT-ER mice with 4-OHT treatment. These cells were either maintained on SCID mice treated with 4-OHT or vehicle. Cells maintained on vehicle eventually developed ALT-dependent resistance. We used microarray to profile telomerase+ tumors vs. ALT+ tumors from the same parental lines.
2012-01-17 | E-GEOD-35044 | biostudies-arrayexpress
Project description:Genomic copy numbers of various generations of Atm-/-TERT-ER mice treated with 4-OHT or vehicle were profiled. Genomic copy numbers of transplanted G3 Atm-/-TERT-ER T-cell lymphomas with telomerase or ALT T-cell lymphomas were developed in various generations of Atm-/-TERT-ER mice with 4-OHT or vehicle treatment. These tumors were profiled with aCGH. G3 Atm-/-TERT-ER tumors were transplanted into SCID mice treated with 4-OHT or vehicle. Cells maintained on vehicle eventually developed ALT-dependent resistance. We used aCGH to profile telomerase+ tumors vs. ALT+ tumors from the same parental lines.
2012-01-17 | E-GEOD-35045 | biostudies-arrayexpress
Project description:Genomic copy numbers of various generations of Atm-/-TERT-ER mice treated with 4-OHT or vehicle were profiled. Genomic copy numbers of transplanted G3 Atm-/-TERT-ER T-cell lymphomas with telomerase or ALT
2012-01-17 | GSE35045 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE35044: Expression profiles of Telomerase+ vs. ALT+ G3 Atm-/-TERT-ER T-cell lymphomas GSE35045: Genomic copy number profiling of different generations of Atm-/-TERT-ER T-cell lymphomas and associated resistant tumors following telomerase inhibition Refer to individual Series
2012-01-17 | E-GEOD-35046 | biostudies-arrayexpress
Project description:The up-regulation of a telomere maintenance mechanism (TMM) is an essential step in cancer progression to escape dysfunctional telomeres, senescence and apoptosis. Paediatric brain tumors frequently exhibit Alternative Lengthening of Telomere (ALT) as active TMM, but the mechanisms involved in the induction of ALT in brain tumor cells are not clear. Here, we report a model of juvenile zebrafish brain tumor that progressively develops ALT. We discovered that reduced expression of tert and increase in Terra expression precedes ALT development. Additionally, tumors show persistent telomeric DNA damage and loss of heterochromatin marks. Comparative analysis of gene expression after the rescue of ALT with telomerase and analysis of telomerase positive paediatric brain cancers showed normalization of telomeric heterochromatin and maintenance of telomere length, with reduced expression of genes of the pre-replicative complex as hallmark. Thus our study identifies telomere maintenance mechanisms as major drivers of DNA replication and chromatin status at telomeres in brain cancers.
2022-07-01 | GSE134135 | GEO
Project description:The aim of this study is to determine the clinical relevance of telomerase activation versus ALT as biomarkers in pre-treatment neuroblastoma, and to assess the potential value of telomerase as a therapeutic target. Therefore, the genomic status of TERT and MYCN was assessed in 457 pretreatment neuroblastomas by fluorescence-in-situ-hybridization. ALT was examined in 273/457 tumors by detection of ALT-associated promyelocytic leukemia nuclear bodies, and TERT expression was determined by 4x44k microarrays in 223 of these. The presence of activated telomerase, i.e., TERT rearrangements, MYCN amplification, or high TERT expression without these alterations, was associated with poorest overall survival, and was an independent prognostic marker in multivariable analyses.
2019-09-16 | E-MTAB-8248 | biostudies-arrayexpress
Project description:A gene expression signature classifying telomerase and ALT immortalisation reveals an hTERT regulatory network and suggests a mesenchymal stem cell origin for ALT Telomere length is maintained by 2 known mechanisms, 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 previously 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 gene expression profiles of liposarcoma tissue samples we refined this signature to 297 genes significantly associated with telomere maintenance mechanism. Network analysis of known direct interactions between genes within this signature revealed a regulatory signalling network consistent with a model of 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. In addition we show evidence to suggest a novel mesenchymal stem cell origin for ALT immortalisation in cell lines and mesenchymal tissues. Keywords: cell type comparison, gene expression
2009-11-02 | GSE14529 | GEO
Project description:A gene expression signature classifying telomerase and ALT immortalisation reveals an hTERT regulatory network and suggests a mesenchymal stem cell origin for ALT Telomere length is maintained by 2 known mechanisms, 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 previously 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 gene expression profiles of liposarcoma tissue samples we refined this signature to 297 genes significantly associated with telomere maintenance mechanism. Network analysis of known direct interactions between genes within this signature revealed a regulatory signalling network consistent with a model of 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. In addition we show evidence to suggest a novel mesenchymal stem cell origin for ALT immortalisation in cell lines and mesenchymal tissues. Keywords: cell type comparison, gene expression
2009-11-02 | GSE14487 | GEO
Project description:The presence of ALT is strongly associated with recurrent cancer-specific somatic inactivating mutations in the ATRX-DAXX chromatin remodeling complex. Here, we generate an ALT-positive adenocarcinoma cell line following functional inactivation of ATRX and telomerase in a telomerase-positive carcinoma cell line.
2019-09-25 | GSE129448 | GEO
Project description:Constitutively active MYC and reactivated telomerase often co-exist in cancers. While the reactivation of telomerase is thought to be essential for replicative immortality, MYC, in conjunction with co-factors, confers several growth advantages to cancer cells. However, it is unclear which co-factors sustain elevated MYC activity in tumors . Here, we identify TERT, the catalytic subunit of telomerase, as a novel regulator of MYC stability in cancers. Binding of TERT to MYC stabilizes its levels on chromatin, contributing to either activation or repression of its target genes. Mechanistically, TERT regulates MYC ubiquitination and stability, and this effect of TERT is independent of its role on telomeres. Genetic inhibition and knocking out of TERT phenocopied the loss of MYC, resulting in reduced disease burden of early- and late-stage MYC-driven murine lymphomas. Conversly, the ectopic expression of TERT could substitute for reduced MYC in these functions. Finally we show that TERT null mice, unlike Terc null mice, show delayed onset of MYC induced lymphomagenesis. Accordingly, inhibiting TERT function in primary human leukemia cells blocked the expression of MYC targets, while Terc depletion had no effects . Based on our data, we conclude that the re-expression of TERT, a direct MYC target in tumors, provides a feed-forward mechanism to potentiate MYC-dependent oncogenesis.
2015-04-23 | GSE60175 | GEO