Detection of the alternative lengthening of telomeres pathway in malignant gliomas for improved molecular diagnosis View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-11

AUTHORS

Anne Fogli, Marie-Véronique Demattei, Laetitia Corset, Catherine Vaurs-Barrière, Emmanuel Chautard, Julian Biau, Jean-Louis Kémény, Catherine Godfraind, Bruno Pereira, Toufik Khalil, Nathalie Grandin, Philippe Arnaud, Michel Charbonneau, Pierre Verrelle

ABSTRACT

Human malignant gliomas exhibit acquisition of either one of two telomere maintenance mechanisms, resulting from either reactivation of telomerase expression or activation of an alternative lengthening of telomeres (ALT) mechanism. In the present study, we analyzed 63 human malignant gliomas for the presence of ALT-specific extrachromosomal circles of telomeric DNA (C-circles) and measured telomerase expression, telomeric DNA content (Telo/Alu method), and telomeric repeat-containing RNAs (TERRA) levels. We also assessed histomolecular markers routinely used in clinical practice. The presence of C-circles significantly correlated with IDH1/2 mutation, MGMT exon 1 methylation, low Ki-67 immunostaining, increased telomeric DNA content, absence of functional ATRX protein and level of HTERT gene expression. In multivariate analysis, we observed a trend to a correlation between elevated TERRA levels and increased survival. Interestingly, the C-circles assay allowed to detect ALT activation in glioblastomas exhibiting wild-type IDH1/2 and ATRX expression. These results suggest that, after the correlations uncovered here have been confirmed on larger numbers of tumors, telomeric markers might be useful in improving diagnosis. They also point out to the utility of using the specific, sensitive and quantitative C-circle and Telo/Alu assays that can work with as few as 30 ng of tumor DNA. More... »

PAGES

381-390

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s11060-017-2585-7

DOI

http://dx.doi.org/10.1007/s11060-017-2585-7

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1090909714

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28755323


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