A majority of cancers (~85%) activate the enzyme telomerase to maintain telomere length over multiple rounds of cellular division. Telomerase-negative cancers activate a distinct, telomerase-independent mechanism of telomere maintenance termed alternative lengthening of telomeres (ALT). ALT uses homologous recombination to maintain telomere length and exhibits features of break-induced DNA replication. In malignant gliomas, the activation of either telomerase or ALT is nearly ubiquitous in pediatric and adult tumors, and the frequency with which these distinct telomere maintenance mechanisms (TMMs) is activated varies according to genetically defined glioma subtypes. In this review, we summarize the current state of the field of TMMs and their relevance to glioma biology and therapy. We review the genetic alterations and molecular mechanisms leading to telomerase activation or ALT induction in pediatric and adult gliomas. With this background, we review emerging evidence on strategies for targeting TMMs for glioma therapy. Finally, we comment on critical gaps and issues for moving the field forward to translate our improved understanding of glioma telomere maintenance into better therapeutic strategies for patients.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11145458 | PMC |
| http://dx.doi.org/10.1093/neuonc/noae016 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Targeted Next-Generation Sequencing in Succinate Dehydrogenase-Deficient GI Stromal Tumor Identifies Actionable Alterations in the PI3K/mTOR Pathway.
JCO Precis Oncol
January 2025
Sarcoma Translational Research Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
Purpose: Less than 5% of GI stromal tumors (GISTs) are driven by the loss of the succinate dehydrogenase (SDH) complex, resulting in a pervasive DNA hypermethylation pattern that leads to unique clinical features. Advanced SDH-deficient GISTs are usually treated with the same therapies targeting KIT and PDGFRA receptors as those used in metastatic GIST. However, these treatments display less activity in the absence of alternative therapeutic options.
View Article and Find Full Text PDFBiomarkers.
Alzheimers Dement
December 2024
University of São Paulo Universidade de São Paulo, São Paulo, Brazil.
Background: The Down Syndrome (DS), also referred to as trisomy of chromosome 21, is a prevalent cause of intellectual disability and also contributes to the acceleration of aging, among other developmental and health concerns. Certain pathological characteristics shared by DS and Alzheimer's Disease (AD) indicate similar commonalities. This study aims to unravel the relationship between the canonical Wnt/pathway, the amyloid precursor protein processing, the telomere shortening in DS individuals.
View Article and Find Full Text PDFThe single-stranded DNA-binding factor SUB1/PC4 alleviates replication stress at telomeres and is a vulnerability of ALT cancer cells.
Proc Natl Acad Sci U S A
January 2025
Département de Biologie, Université de Sherbrooke, Sherbrooke, QC J1K 2R1, Canada.
To achieve replicative immortality, cancer cells must activate telomere maintenance mechanisms. In 10 to 15% of cancers, this is enabled by recombination-based alternative lengthening of telomeres pathways (ALT). ALT cells display several hallmarks including heterogeneous telomere length, extrachromosomal telomeric repeats, and ALT-associated PML bodies.
View Article and Find Full Text PDFSuppressing the Aging Phenotype of Mesenchymal Stromal Cells: Are We Ready for Clinical Translation?
Biomedicines
December 2024
Department of Surgical Sciences, CIR-Dental School, University of Turin, 10126 Turin, Italy.
Mesenchymal stem/stromal cells (MSCs) are involved in the maintenance and regeneration of a large variety of tissues due to their stemness and multi-lineage differentiation capability. Harnessing these advantageous features, a flurry of clinical trials have focused on MSCs to treat different pathologies, but only few protocols have received regulatory approval so far. Among the various causes hindering MSCs' efficacy is the emergence of cellular senescence, which has been correlated with specific characteristics, such as morphological and epigenetic alterations, DNA damage, ROS production, mitochondrial dysfunction, telomere shortening, non-coding RNAs, loss of proteostasis, and a peculiar senescence-associated secretory phenotype.
View Article and Find Full Text PDFIGF2BPs-regulated TIN2 confers the malignant biological behaviors of gastric cancer cells.
Tissue Cell
December 2024
Department of Pathology, The Fourth Hospital of Changsha, Changsha, Hunan 410006, PR China. Electronic address:
Background: Telomere maintenance is an important feature of tumor cells. Telomeric-repeat binding factor 1 interaction nuclear protein 2 (TIN2), a key member of the shelterin proteins, functions in regulating telomere structure, length and function. Our work sought to investigate the role of TIN2 in controlling gastric cancer (GC) malignant biological behaviors.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!