Journal Article

Detection of alternative lengthening of telomeres mechanism on tumor sections

Claude, Eloïse, Marbaix, Etienne, de Ville de Goyet, Maëlle, Decottignies, Anabelle, de Lhoneux, Guillaume, Boulanger, Cécile, Brichard, Bénédicte, Van Damme, An, Pierreux, Christophe E.

2021

Overview

The vast majority of adult cancer cells achieve cellular immortality by activating a telomere maintenance mechanism (TMM). While this is mostly achieved by the de-silencing of h TERT telomerase gene expression, an alternative homologous recombination-based and telomerase-independent mechanism, known as ALT (Alternative Lengthening of Telomeres), is frequently activated in a subset of tumors, including paediatric cancers. Being absent from normal cells, the ALT mechanism offers interesting perspectives for new targeted cancer therapies. To date, however, the development of better translationally applicable tools for ALT detection in tumor sections is still needed. Here, using a newly derived ALT-positive cancer cell mouse xenograft model, we extensively examined how the previously known ALT markers could be used as reliable tools for ALT diagnosis in tumor sections. We found that, together with the detection of ultra-bright telomeric signals (UBS), an ALT hallmark, native telomeric FISH, that detects single-stranded C-rich telomeric DNA, provides a very sensitive and robust tool for ALT diagnosis in tissues. We applied these assays to paediatric tumor samples and readily identified three ALT-positive tumors for which the TMM was confirmed by the gold-standard C-circle amplification assay. Although the latter offers a robust assay for ALT detection in the context of research laboratories, it is more difficult to set up in histopathological laboratories and could therefore be conveniently replaced by the combination of UBS detection and native telomeric FISH.

• Publisher: Springer Singapore,Springer Nature B.V,Springer
• Subject: ALT xenograft / Alternative lengthening of telomeres / Biomedical and Life Sciences / Biomedical Engineering/Biotechnology / Biomedicine / Bone cancer / Brain cancer / Cancer therapies / Gene expression / Localization / Molecular Medicine / Native telomeric FISH / Neuroblastoma / Paediatric tumor / Pediatrics / Sarcoma / Telomerase / Telomere / Tumors