scholarly journals Evidence for alternative lengthening of telomeres in liposarcomas in the absence of ALT-associated PML bodies

2008 ◽  
Vol 122 (11) ◽  
pp. 2414-2421 ◽  
Author(s):  
Jennie N. Jeyapalan ◽  
Aaron Mendez-Bermudez ◽  
Nadia Zaffaroni ◽  
Yuri E. Dubrova ◽  
Nicola J. Royle
Keyword(s):  
Alternative Lengthening Of Telomeres ◽  
Alternative Lengthening ◽  
Pml Bodies

scholarly journals HP1-Mediated Formation of Alternative Lengthening of Telomeres-Associated PML Bodies Requires HIRA but Not ASF1a

PLoS ONE ◽  
2011 ◽  
Vol 6 (2) ◽  
pp. e17036 ◽  
Author(s):  
Wei-Qin Jiang ◽  
Akira Nguyen ◽  
Ying Cao ◽  
Andy C.-M. Chang ◽  
Roger R. Reddel
Keyword(s):  
Alternative Lengthening Of Telomeres ◽  
Alternative Lengthening ◽  
Pml Bodies

scholarly journals Induction of alternative lengthening of telomeres-associated PML bodies by p53/p21 requires HP1 proteins

2009 ◽  
Vol 185 (5) ◽  
pp. 797-810 ◽  
Author(s):  
Wei-Qin Jiang ◽  
Ze-Huai Zhong ◽  
Akira Nguyen ◽  
Jeremy D. Henson ◽  
Christian D. Toouli ◽  
...  
Keyword(s):  
Growth Arrest ◽  
Nuclear Bodies ◽  
Activity Level ◽  
Heterochromatin Protein 1 ◽  
Alternative Lengthening Of Telomeres ◽  
Heterochromatin Protein ◽  
Alternative Lengthening ◽  
Pml Bodies ◽  
A Cell ◽  
Hp1 Proteins

Alternative lengthening of telomeres (ALT) is a recombination-mediated process that maintains telomeres in telomerase-negative cancer cells. In asynchronously dividing ALT-positive cell populations, a small fraction of the cells have ALT-associated promyelocytic leukemia nuclear bodies (APBs), which contain (TTAGGG)n DNA and telomere-binding proteins. We found that restoring p53 function in ALT cells caused p21 up-regulation, growth arrest/senescence, and a large increase in cells containing APBs. Knockdown of p21 significantly reduced p53-mediated induction of APBs. Moreover, we found that heterochromatin protein 1 (HP1) is present in APBs, and knockdown of HP1α and/or HP1γ prevented p53-mediated APB induction, which suggests that HP1-mediated chromatin compaction is required for APB formation. Therefore, although the presence of APBs in a cell line or tumor is an excellent qualitative marker for ALT, the association of APBs with growth arrest/senescence and with “closed” telomeric chromatin, which is likely to repress recombination, suggests there is no simple correlation between ALT activity level and the number of APBs or APB-positive cells.

scholarly journals Coexistence of Alternative Lengthening of Telomeres and Telomerase in hTERT-Transfected GM847 Cells

2001 ◽  
Vol 21 (12) ◽  
pp. 3862-3875 ◽  
Author(s):  
Kilian Perrem ◽  
Lorel M. Colgin ◽  
Axel A. Neumann ◽  
Thomas R. Yeager ◽  
Roger R. Reddel
Keyword(s):  
Cell Line ◽  
Telomerase Activity ◽  
Promyelocytic Leukemia ◽  
Tumor Cell Lines ◽  
Hybrid Cells ◽  
Alternative Lengthening Of Telomeres ◽  
Positive Tumor Cell ◽  
Alternative Lengthening ◽  
Pml Bodies ◽  
Population Doublings

ABSTRACT It has been shown previously that some immortalized human cells maintain their telomeres in the absence of significant levels of telomerase activity by a mechanism referred to as alternative lengthening of telomeres (ALT). Cells utilizing ALT have telomeres of very heterogeneous length, ranging from very short to very long. Here we report the effect of telomerase expression in the ALT cell line GM847. Expression of exogenous hTERT in GM847 (GM847/hTERT) cells resulted in lengthening of the shortest telomeres; this is the first evidence that expression of hTERT in ALT cells can induce telomerase that is active at the telomere. However, rapid fluctuation in telomere length still occurred in the GM847/hTERT cells after more than 100 population doublings. Very long telomeres and ALT-associated promyelocytic leukemia (PML) bodies continued to be generated, indicating that telomerase activity induced by exogenous hTERT did not abolish the ALT mechanism. In contrast, when the GM847 cell line was fused with two different telomerase-positive tumor cell lines, the ALT phenotype was repressed in each case. These hybrid cells were telomerase positive, and the telomeres decreased in length, very rapidly at first and then at the rate seen in telomerase-negative normal cells. Additionally, ALT-associated PML bodies disappeared. After the telomeres had shortened sufficiently, they were maintained at a stable length by telomerase. Together these data indicate that the telomerase-positive cells contain a factor that represses the ALT mechanism but that this factor is unlikely to be telomerase. Further, the transfection data indicate that ALT and telomerase can coexist in the same cells.

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.

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