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Review
. 2021 Jul 16;23(9):106.
doi: 10.1007/s11912-021-01096-w.

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

Claudio Luchini  1 , Rita T Lawlor  2 , Samantha Bersani  2 , Caterina Vicentini  2 , Gaetano Paolino  2 , Paola Mattiolo  1 , Antonio Pea  3 , Sara Cingarlini  4 , Michele Milella  4 , Aldo Scarpa  5   6
Affiliations
Review

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

Claudio Luchini et al. Curr Oncol Rep. .

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. 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.

Keywords: ALT; ATRX; DAXX; PanNET; Pancreatic neuroendocrine tumors.

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Conflict of interest statement

Claudia Luchini has received compensation from BioScience Communications for expert testimony on microsatellite instability. Rita T. Lawlor declares that she has no conflict of interest. Samantha Bersani declares that she has no conflict of interest. Caterina Vicentini declares that she has no conflict of interest. Gaetano Paolino declares that he has no conflict of interest. Paola Mattiolo declares that she has no conflict of interest. Antonio Pea declares that he has no conflict of interest. Sara Cingarlini declares that she has no conflict of interest. Michele Milella declares that he has no conflict of interest. Aldo Scarpa declares that he has no conflict of interest.

Figures

Fig. 1
Fig. 1
A classic example of a pancreatic neuroendocrine tumor with the activation of the ALT mechanism analyzed with telomere-specific FISH. The presence of large ultrabright telomere FISH signals (arrows) is the pictorial marker of the activated alternative lengthening of telomere mechanism (A ×4 original magnification; B ×10)
Fig. 2
Fig. 2
Representation of two paradigmatic cases of pancreatic neuroendocrine tumors, one with retained expression of DAXX/ATRX at immunohistochemistry (A hematoxylin-eosin, B DAXX immunostaining, C ATRX immunostaining; original magnification ×10) and one with DAXX loss (D hematoxylin-eosin, E DAXX immunostaining, highlighting loss of nuclear expression; original magnification ×20)
See this image and copyright information in PMC

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