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Open Access 01-12-2019 | Neurofibromatosis Type 1 | Research

Telomere alterations in neurofibromatosis type 1-associated solid tumors

Authors: Fausto J. Rodriguez, Mindy K. Graham, Jacqueline A. Brosnan-Cashman, John R. Barber, Christine Davis, M. Adelita Vizcaino, Doreen N. Palsgrove, Caterina Giannini, Melike Pekmezci, Sonika Dahiya, Murat Gokden, Michael Noë, Laura D. Wood, Christine A. Pratilas, Carol D. Morris, Allan Belzberg, Jaishri Blakeley, Christopher M. Heaphy

Published in: Acta Neuropathologica Communications | Issue 1/2019

Abstract

The presence of Alternative lengthening of telomeres (ALT) and/or ATRX loss, as well as the role of other telomere abnormalities, have not been formally studied across the spectrum of NF1-associated solid tumors. Utilizing a telomere-specific FISH assay, we classified tumors as either ALT-positive or having long (without ALT), short, or normal telomere lengths. A total of 426 tumors from 256 NF1 patients were evaluated, as well as 99 MPNST tumor samples that were sporadic or of unknown NF1 status. In the NF1-glioma dataset, ALT was present in the majority of high-grade gliomas: 14 (of 23; 60%) in contrast to only 9 (of 47; 19%) low-grade gliomas (p = 0.0009). In the subset of ALT-negative glioma cases, telomere lengths were estimated and we observed 17 (57%) cases with normal, 12 (40%) cases with abnormally long, and only 1 (3%) case with short telomeres. In the NF1-associated malignant nerve sheath tumor (NF1-MPNST) set (n = 75), ALT was present in 9 (12%). In the subset of ALT-negative NF1-MPNST cases, telomeres were short in 9 (38%), normal in 14 (58%) and long in 1 (3%). In the glioma set, overall survival was significantly decreased for patients with ALT-positive tumors (p < 0.0001). In the NF1-MPNST group, overall survival was superior for patients with tumors with short telomeres (p = 0.003). ALT occurs in a subset of NF1-associated solid tumors and is usually restricted to malignant subsets. In contrast, alterations in telomere lengths are more prevalent than ALT.

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Title: Telomere alterations in neurofibromatosis type 1-associated solid tumors
Authors: Fausto J. Rodriguez
Mindy K. Graham
Jacqueline A. Brosnan-Cashman
John R. Barber
Christine Davis
M. Adelita Vizcaino
Doreen N. Palsgrove
Caterina Giannini
Melike Pekmezci
Sonika Dahiya
Murat Gokden
Michael Noë
Laura D. Wood
Christine A. Pratilas
Carol D. Morris
Allan Belzberg
Jaishri Blakeley
Christopher M. Heaphy
Publication date: 01-12-2019
Publisher: BioMed Central
Keywords: Neurofibromatosis Type 1
Glioma
Glioma
Glioma
Solid Tumor
Published in: Acta Neuropathologica Communications / Issue 1/2019
Electronic ISSN: 2051-5960
DOI: https://doi.org/10.1186/s40478-019-0792-5

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Springer Medicine

Telomere alterations in neurofibromatosis type 1-associated solid tumors

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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