Unknown,Transcriptomics,Genomics,Proteomics

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Telomerase is a prognostic marker of poor outcome and a therapeutic target in neuroblastoma

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

SUBMITTER: Christoph Bartenhagen

PROVIDER: E-MTAB-8248 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:We generated gene expression profiles from 498 primary neuroblastomas using RNA-Seq and microarrays. We sought to systematically evaluate the capability of RNA deep-sequencing (RNA-Seq)-based classification for clinical endpoint prediction in comparison to microarray-based ones. The neuroblastoma cohort was randomly divided into training and validation sets, and 360 predictive models on six clinical endpoints were generated and evaluated. While prediction performances did not differ considerably between the two technical platforms, the RNA-Seq data processing pipelines, or feature levels (i.e., gene, transcript, and exon junction levels), RNA-Seq models based on the AceView database performed best on most endpoints. Collectively, our study reveals an unprecedented complexity of the neuroblastoma transcriptome, and provides guidelines for the development of gene expression-based predictive classifiers using high-throughput technologies. Sample clinical characteristics definitions: dataset: Expression data set used for classification training (1) or validation (2) Sex: M = male; F= female age at diagnosis: the age in days at diagnosis mycn status: Amplification status of the MYCN proto-oncogene (amplified = 1, no amplification = 0; no information = N/A) high risk: Clinically considered as high-risk neuroblastoma (yes=1, no= 0) INSS stage: disease stage according to International Neuroblastoma Staging System (INSS) (1, 2, 3, 4 and 4S) class label: Maximally divergent disease courses - unfavorable (= 1): patient died despite intensive chemotherapy, favorable (=0): patient survived without chemotharapy for at least 1000 days post diagnosis; not applicable (N/A) progression: Occurrence of a tumor progression event (yes=1; no=0) death from disease: Occurrence of death from the disease (yes=1; no=0) Gene expression of 498 neuroblastoma samples was quantified by RNA sequencing as well as by microarray analyses in order to understand the neuroblastoma transcriptome and predict clinical endpoints.

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Telomerase is a prognostic marker of poor outcome and a therapeutic target in neuroblastoma

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