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ALT: A Multi-Faceted Phenomenon.

ABSTRACT: One of the hallmarks of cancer cells is their indefinite replicative potential, made possible by the activation of a telomere maintenance mechanism (TMM). The majority of cancers reactivate the reverse transcriptase, telomerase, to maintain their telomere length but a minority (10% to 15%) utilize an alternative lengthening of telomeres (ALT) pathway. Here, we review the phenotypes and molecular markers specific to ALT, and investigate the significance of telomere mutations and sequence variation in ALT cell lines. We also look at the recent advancements in understanding the different mechanisms behind ALT telomere elongation and finally, the progress made in identifying potential ALT-targeted therapies, including those already in use for the treatment of both hematological and solid tumors.

SUBMITTER: Sommer A

PROVIDER: S-EPMC7073516 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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ALT: A Multi-Faceted Phenomenon.

Sommer Aurore A Royle Nicola J NJ

Genes 20200127 2

One of the hallmarks of cancer cells is their indefinite replicative potential, made possible by the activation of a telomere maintenance mechanism (TMM). The majority of cancers reactivate the reverse transcriptase, telomerase, to maintain their telomere length but a minority (10% to 15%) utilize an alternative lengthening of telomeres (ALT) pathway. Here, we review the phenotypes and molecular markers specific to ALT, and investigate the significance of telomere mutations and sequence variatio ...[more]

PMID: 32012790

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Project description:Background and aimsThe new coronavirus disease (COVID-19) is a systemic disease. Mounting evidence depict signs and symptoms involving multiple organs, most of which supported by pathological data. A plausible link to these manifestations is vascular and endothelial dysfunction/damage. However, much of the current knowledge relies on opinion and incipient evidence. We aim to objectively appraise current evidence on the association between COVID-19 and vascular disease, specifically endotheliitis and vasculitis.MethodsTwo researchers independently entered the search terms COVID-19 OR SARS-CoV-2 AND vasculitis, endotheliitis OR endothelium in the following online platforms: MedRxiv and LitCovid (PubMed). The search period was set from November 1, 2019 to August 28, 2020. Manuscripts with unavailable full texts, not in English, mainly on pre-clinical data, presenting only study designs or not directly related to the topics of this review were excluded. Retrospective and prospective studies, especially longitudinal ones, were given priority to the purpose of this review. Since there was paucity of prospective controlled evidence, case reports/series were also considered.ResultsA total of 318 manuscripts were initially found. Sixty-seven (21%) were excluded: 59 (18.5%) met exclusion criteria and 8 (2.5%) were duplicates. One hundred and forty-two manuscripts (44,6%) did not provide original data and were also excluded: 35 (11%) were comments, 108 (33.9%) reviews; 1 (0.3%) position paper. One hundred and seven (33.6%) studies were considered for the present scoping review: 81 (25,5%) case reports/series; 18 (5.7%) prospective; 8 (2.5%) retrospective. Viral inclusions in endothelial cells, mononuclear cell infiltrates in the intima of small vessels and markers of endothelial cell apoptosis were demonstrated. Specificities of COVID-19 may lead to diverse vascular manifestations in different levels of the vascular bed.ConclusionsEvidence indicates that COVID-19 targets vasculature and endothelium. However, high quality data is still lacking and studies with prospective designs and appropriately matched controls are needed.

Dataset Information

ALT: A Multi-Faceted Phenomenon.

Publications

ALT: A Multi-Faceted Phenomenon.

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