scholarly journals Alternative lengthening of telomeres is mechanistically linked to potential therapeutic vulnerability in the stem‐like subtype of gastric cancer

2021 ◽  
Vol 11 (9) ◽  
Author(s):  
Ji‐Yong Sung ◽  
Jae‐Ho Cheong
Keyword(s):  
Gastric Cancer ◽  
Alternative Lengthening Of Telomeres ◽  
Alternative Lengthening

scholarly journals Alternative lengthening of telomeres in childhood neuroblastoma from genome to proteome

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sabine A. Hartlieb ◽  
Lina Sieverling ◽  
Michal Nadler-Holly ◽  
Matthias Ziehm ◽  
Umut H. Toprak ◽  
...  
Keyword(s):  
High Frequency ◽  
Clinical Course ◽  
Population Based ◽  
Telomeric Repeat ◽  
Telomere Maintenance ◽  
Study Cohort ◽  
Alternative Lengthening Of Telomeres ◽  
Course Of Disease ◽  
Low Protein ◽  
Alternative Lengthening

AbstractTelomere maintenance by telomerase activation or alternative lengthening of telomeres (ALT) is a major determinant of poor outcome in neuroblastoma. Here, we screen for ALT in primary and relapsed neuroblastomas (n = 760) and characterize its features using multi-omics profiling. ALT-positive tumors are molecularly distinct from other neuroblastoma subtypes and enriched in a population-based clinical sequencing study cohort for relapsed cases. They display reduced ATRX/DAXX complex abundance, due to either ATRX mutations (55%) or low protein expression. The heterochromatic histone mark H3K9me3 recognized by ATRX is enriched at the telomeres of ALT-positive tumors. Notably, we find a high frequency of telomeric repeat loci with a neuroblastoma ALT-specific hotspot on chr1q42.2 and loss of the adjacent chromosomal segment forming a neo-telomere. ALT-positive neuroblastomas proliferate slowly, which is reflected by a protracted clinical course of disease. Nevertheless, children with an ALT-positive neuroblastoma have dismal outcome.

scholarly journals Alternative lengthening of telomeres and loss of ATRX are frequent events in pleomorphic and dedifferentiated liposarcomas

2015 ◽  
Vol 28 (8) ◽  
pp. 1064-1073 ◽  
Author(s):  
Jen-Chieh Lee ◽  
Yung-Ming Jeng ◽  
Jau-Yu Liau ◽  
Jia-Huei Tsai ◽  
Hung-Han Hsu ◽  
...  
Keyword(s):  
Alternative Lengthening Of Telomeres ◽  
Alternative Lengthening

scholarly journals Nuclear receptors regulate alternative lengthening of telomeres through a novel noncanonical FANCD2 pathway

2019 ◽  
Vol 5 (10) ◽  
pp. eaax6366 ◽  
Author(s):  
Mafei Xu ◽  
Jun Qin ◽  
Leiming Wang ◽  
Hui-Ju Lee ◽  
Chung-Yang Kao ◽  
...  
Keyword(s):  
Nuclear Receptors ◽  
Direct Interaction ◽  
Telomere Maintenance ◽  
Telomeric Dna ◽  
Core Complex ◽  
Alternative Lengthening Of Telomeres ◽  
Independent Manner ◽  
Replication Complex ◽  
Alternative Lengthening ◽  
Key Steps

Alternative lengthening of telomeres (ALT) is known to use homologous recombination (HR) to replicate telomeric DNA in a telomerase-independent manner. However, the detailed process remains largely undefined. It was reported that nuclear receptors COUP-TFII and TR4 are recruited to the enriched GGGTCA variant repeats embedded within ALT telomeres, implicating nuclear receptors in regulating ALT activity. Here, we identified a function of nuclear receptors in ALT telomere maintenance that involves a direct interaction between COUP-TFII/TR4 and FANCD2, the key protein in the Fanconi anemia (FA) DNA repair pathway. The COUP-TFII/TR4-FANCD2 complex actively induces the DNA damage response by recruiting endonuclease MUS81 and promoting the loading of the PCNA-POLD3 replication complex in ALT telomeres. Furthermore, the COUP-TFII/TR4-mediated ALT telomere pathway does not require the FA core complex or the monoubiquitylation of FANCD2, key steps in the canonical FA pathway. Thus, our findings reveal that COUP-TFII/TR4 regulates ALT telomere maintenance through a novel noncanonical FANCD2 pathway.

Inhibition of telomerase induces alternative lengthening of telomeres during human esophageal carcinogenesis

2013 ◽  
Vol 206 (11) ◽  
pp. 374-386 ◽  
Author(s):  
Angela Queisser ◽  
Steffen Heeg ◽  
Michaela Thaler ◽  
Alexander von Werder ◽  
Oliver G. Opitz
Keyword(s):  
Alternative Lengthening Of Telomeres ◽  
Alternative Lengthening ◽  
Esophageal Carcinogenesis
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