The Roles of Telomeres and Telomerase in Early Developmental Processes and Cancer Development

A special issue of Biology (ISSN 2079-7737). This special issue belongs to the section "Medical Biology".

Deadline for manuscript submissions: closed (31 July 2021) | Viewed by 2649

Special Issue Editor

Department of Biochemistry, College of Medicine, Gyeongsang National University, Jinju 52727, Korea
Interests: senescence; aging; age-associated diseases

Special Issue Information

Dear Colleagues,

Telomere and telomerase have received a great amount of attention from many researchers, as they play important roles in replicative senescence and aging, which are closely related to cancer transformation. Telomere caps chromosome ends to keep genomic integrity from incomplete DNA replication. Since any recombination or fusion of telomeres could trigger deleterious outcomes, mammalian cells have multiple safety measures, such as shelterin complexes and looping structures. Recent reports also suggest that telomeric heterochromatin could regulate distal gene expression via changes in genome architecture.

Telomerase extends telomeric repeats so that enzymatic activity is indispensable in the propagation of cancer cells and extensive cell divisions in early development. While telomerase activity is expressed during the first trimester in human development, it is not precisely known what causes its repression in somatic cells. It is largely unknown what cis- and trans-acting factors could regulate transcription and post-transcriptional regulation of the TERT. Reactivation telomerase or ALT (alternative lengthening of telomeres) still await extensive studies for understanding and therapeutic intervention of cancer.

For this Special Issue, we will cover the biology of the telomere in early developmental processes and cancer development. Regulation of telomere during aging will also be discussed. This Special Issue also invites studies on transcription and post-transcriptional regulation of TERT as well as post-translational regulation of telomerase activity. Mechanistic insights into telomerase reactivation and ALT will also be covered in this Special Issue.

Dr. Wanil Kim
Guest Editor

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Keywords

  • telomere
  • telomerase
  • alternative lengthening of telomeres
  • replicative senescence
  • telomerase reactivation

Published Papers (1 paper)

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9 pages, 7704 KiB  
Case Report
A Multifocal Pediatric Papillary Thyroid Carcinoma (PTC) Harboring the AGK-BRAF and RET/PTC3 Fusion in a Mutually Exclusive Pattern Reveals Distinct Levels of Genomic Instability and Nuclear Organization
by Luiza Sisdelli, Maria Isabel V. Cordioli, Fernanda Vaisman, Osmar Monte, Carlos A. Longui, Adriano N. Cury, Monique O. Freitas, Aline Rangel-Pozzo, Sabine Mai and Janete M. Cerutti
Biology 2021, 10(2), 125; https://doi.org/10.3390/biology10020125 - 05 Feb 2021
Cited by 4 | Viewed by 2333
Abstract
The spectrum and incidence of gene fusions in papillary thyroid carcinoma (PTC) can differ significantly depending on the age of onset, histological subtype or radiation exposure history. In sporadic pediatric PTC, RET/PTC1-3 and AGK-BRAF fusions are common genetic alterations. The role of RET/PTC [...] Read more.
The spectrum and incidence of gene fusions in papillary thyroid carcinoma (PTC) can differ significantly depending on the age of onset, histological subtype or radiation exposure history. In sporadic pediatric PTC, RET/PTC1-3 and AGK-BRAF fusions are common genetic alterations. The role of RET/PTC as a prognostic marker in pediatric PTC is still under investigation. We recently showed that AGK-BRAF fusion is prevalent in young patients (mean 10 years) and associated with specific and aggressive pathological features such as multifocality and lung metastasis. In this pilot study, we report a unique patient harboring three different foci: the first was positive for AGK-BRAF fusion, the second was positive for just RET/PTC3 fusion and the third was negative for both rearrangements. To investigate whether AGK-BRAF and RET/PTC3 are associated with genomic instability and chromatin modifications, we performed quantitative fluorescence in situ hybridization (Q-FISH) of telomere repeats followed by 3D imaging analysis and 3D super-resolution Structured Illumination Microscopy (3D-SIM) to analyze the DNA structure from the foci. We demonstrated in this preliminary study that AGK-BRAF is likely associated with higher levels of telomere-related genomic instability and chromatin remodeling in comparison with RET/PTC3 foci. Our results suggest a progressive disruption in chromatin structure in AGK-BRAF-positive cells, which might explain a more aggressive disease outcome in patients harboring this rearrangement. Full article
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