Alternative Lengthening of Telomeres (ALT) and Telomerase Reverse Transcriptase Promoter Methylation in Recurrent Adult and Primary Pediatric Pituitary Neuroendocrine Tumors

2022 ◽  
Author(s):  
Hiba Alzoubi ◽  
Simone Minasi ◽  
Francesca Gianno ◽  
Manila Antonelli ◽  
Francesca Belardinilli ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Neuroendocrine Tumors ◽  
Promoter Methylation ◽  
Telomerase Reverse Transcriptase ◽  
Alternative Lengthening Of Telomeres ◽  
Alternative Lengthening

Prognostic Value of Alternative Lengthening of Telomeres–Associated Biomarkers in Uterine Sarcoma and Uterine Carcinosarcoma

2012 ◽  
Vol 22 (3) ◽  
pp. 434-441 ◽  
Author(s):  
Yoo-Kyung Lee ◽  
Noh-Hyun Park ◽  
Hyunsook Lee
Keyword(s):  
Reverse Transcriptase ◽  
Uterine Sarcoma ◽  
Significant Feature ◽  
Telomerase Reverse Transcriptase ◽  
Alternative Lengthening Of Telomeres ◽  
Human Telomerase Reverse Transcriptase ◽  
Poor Prognostic Factor ◽  
Uterine Sarcomas ◽  
Alternative Lengthening ◽  
Human Telomerase

ObjectiveA subset of cancer cells maintains telomere lengths in a telomerase-independent manner known as the alternative lengthening of telomeres (ALT). The goal of this study was to evaluate the frequency of ALT in uterine sarcoma and carcinosarcoma and to assess its association with clinical parameters.MethodsRetrospectively collected paraffin blocks from 41 patients with uterine sarcomas and carcinosarcomas were analyzed for ALT-associated promyelocytic leukemia bodies (APBs), which are a significant feature of ALT cells, using combined immunofluorescence and telomere fluorescence in situ hybridization. In addition, a C-circle assay and human telomerase reverse transcriptase immunohistochemistry were performed to support these results.ResultsThe APB assay and C-circle assay indicated that 46.3% (19/41 cases) and 36.4% (8/22 cases) of sarcomas of the uterus, respectively, were positive for ALT. Alternative lengthening of telomerase positivity was correlated with high-grade uterine sarcoma and parameters indicative of an aggressive tumor, such as tumor size (P= 0.033) and mitotic index (P= 0.001); ALT positivity was negatively correlated with human telomerase reverse transcriptase reactivity (P= 0.036). In a survival analysis, the presence of APBs was found to be a poor prognostic factor for disease-free survival (P= 0.018) and overall survival (P= 0.021).ConclusionsAlternative lengthening of telomeres is a prevalent mechanism in uterine sarcomas and carcinosarcomas and is associated with the aggressiveness of the tumor and tumor progression. Importantly, ALT positivity is an indicator of poor prognosis for patients with uterine sarcoma and carcinosarcoma.

scholarly journals Alternative Lengthening of Telomeres and Chromatin Status

Genes ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 45 ◽  
Author(s):  
Ion Udroiu ◽  
Antonella Sgura
Keyword(s):  
Homologous Recombination ◽  
Reverse Transcriptase ◽  
Spatial Heterogeneity ◽  
Telomere Length ◽  
Epigenetic Modifications ◽  
Alternative Lengthening Of Telomeres ◽  
Telomere Elongation ◽  
Alternative Lengthening ◽  
Alt Activity

Telomere length is maintained by either telomerase, a reverse transcriptase, or alternative lengthening of telomeres (ALT), a mechanism that utilizes homologous recombination (HR) proteins. Since access to DNA for HR enzymes is regulated by the chromatin status, it is expected that telomere elongation is linked to epigenetic modifications. The aim of this review is to elucidate the epigenetic features of ALT-positive cells. In order to do this, it is first necessary to understand the telomeric chromatin peculiarities. So far, the epigenetic nature of telomeres is still controversial: some authors describe them as heterochromatic, while for others, they are euchromatic. Similarly, ALT activity should be characterized by the loss (according to most researchers) or formation (as claimed by a minority) of heterochromatin in telomeres. Besides reviewing the main works in this field and the most recent findings, some hypotheses involving the role of telomere non-canonical sequences and the possible spatial heterogeneity of telomeres are given.

scholarly journals Alternative lengthening of telomeres and ATRX/DAXX loss can be reliably detected in FNAs of pancreatic neuroendocrine tumors

2017 ◽  
Vol 125 (7) ◽  
pp. 544-551 ◽  
Author(s):  
Christopher J. VandenBussche ◽  
Derek B. Allison ◽  
Mindy K. Graham ◽  
Vivek Charu ◽  
Anne Marie Lennon ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Pancreatic Neuroendocrine Tumors ◽  
Alternative Lengthening Of Telomeres ◽  
Alternative Lengthening

scholarly journals Alternative Lengthening of Telomeres (ALT) in Pancreatic Neuroendocrine Tumors: Ready for Prime-Time in Clinical Practice?

2021 ◽  
Vol 23 (9) ◽  
Author(s):  
Claudio Luchini ◽  
Rita T. Lawlor ◽  
Samantha Bersani ◽  
Caterina Vicentini ◽  
Gaetano Paolino ◽  
...  
Keyword(s):  
Clinical Practice ◽  
High Risk ◽  
Neuroendocrine Tumors ◽  
Tumor Biology ◽  
Specific Marker ◽  
Fish Analysis ◽  
Pancreatic Neuroendocrine Tumors ◽  
Alternative Lengthening Of Telomeres ◽  
Alternative Lengthening ◽  
Pancreatic Origin

Abstract Purpose of Review Alternative lengthening of telomeres (ALT) is a telomerase-independent mechanism used by some types of malignancies, including pancreatic neuroendocrine tumors, to overcome the issue of telomere shortening, thus supporting tumor growth and cell proliferation. This review is focused on the most important achievements and opportunities deriving from ALT assessment in PanNET onco-pathology, highlighting the most promising fields in which such biomarker could be implemented in clinical practice. Recent Findings In pancreatic neuroendocrine tumors (PanNET), ALT is strongly correlated with the mutational status of two chromatin remodeling genes, DAXX and ATRX. Recent advances in tumor biology permitted to uncover important roles of ALT in the landscape of PanNET, potentially relevant for introducing this biomarker into clinical practice. Indeed, ALT emerged as a reliable indicator of worse prognosis for PanNET, helping in clinical stratification and identification of “high-risk” patients. Furthermore, it is a very specific marker supporting the pancreatic origin of neuroendocrine neoplasms and can be used for improving the diagnostic workflow of patients presenting with neuroendocrine metastasis from unknown primary. The activation of this process can be determined by specific FISH analysis. Summary ALT should be introduced in clinical practice for identifying “high-risk” PanNET patients and improving their clinical management, and as a marker of pancreatic origin among neuroendocrine tumors.

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