Telomere alterations in neurofibromatosis type 1-associated solid tumors

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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Number of pages1
JournalActa Neuropathologica Communications
Volume7
Issue number1
DOIs
StatePublished - Aug 28 2019

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Telomere Homeostasis
Neurofibromatosis 1
Telomere
Glioma
Neurilemmoma
Neoplasms
Nerve Sheath Neoplasms
Survival

Keywords

  • Alternative lengthening of telomeres
  • ATRX
  • Glioma
  • MPNST
  • NF1

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Cite this

Rodriguez, F. J., Graham, M. K., Brosnan-Cashman, J. A., Barber, J. R., Davis, C., Vizcaino, M. A., ... Heaphy, C. M. (2019). Telomere alterations in neurofibromatosis type 1-associated solid tumors. Acta Neuropathologica Communications, 7(1). https://doi.org/10.1186/s40478-019-0792-5

Telomere alterations in neurofibromatosis type 1-associated solid tumors. / Rodriguez, Fausto J.; Graham, Mindy K.; Brosnan-Cashman, Jacqueline A.; Barber, John R.; Davis, Christine; Vizcaino, M. Adelita; Palsgrove, Doreen N.; Giannini, Caterina; Pekmezci, Melike; Dahiya, Sonika; Gokden, Murat; Noë, Michael; Wood, Laura D.; Pratilas, Christine A.; Morris, Carol D.; Belzberg, Allan; Blakeley, Jaishri; Heaphy, Christopher M.

In: Acta Neuropathologica Communications, Vol. 7, No. 1, 28.08.2019.

Research output: Contribution to journalArticle

Rodriguez, FJ, Graham, MK, Brosnan-Cashman, JA, Barber, JR, Davis, C, Vizcaino, MA, Palsgrove, DN, Giannini, C, Pekmezci, M, Dahiya, S, Gokden, M, Noë, M, Wood, LD, Pratilas, CA, Morris, CD, Belzberg, A, Blakeley, J & Heaphy, CM 2019, 'Telomere alterations in neurofibromatosis type 1-associated solid tumors', Acta Neuropathologica Communications, vol. 7, no. 1. https://doi.org/10.1186/s40478-019-0792-5
Rodriguez FJ, Graham MK, Brosnan-Cashman JA, Barber JR, Davis C, Vizcaino MA et al. Telomere alterations in neurofibromatosis type 1-associated solid tumors. Acta Neuropathologica Communications. 2019 Aug 28;7(1). https://doi.org/10.1186/s40478-019-0792-5
Rodriguez, Fausto J. ; Graham, Mindy K. ; Brosnan-Cashman, Jacqueline A. ; Barber, John R. ; Davis, Christine ; Vizcaino, M. Adelita ; Palsgrove, Doreen N. ; Giannini, Caterina ; Pekmezci, Melike ; Dahiya, Sonika ; Gokden, Murat ; Noë, Michael ; Wood, Laura D. ; Pratilas, Christine A. ; Morris, Carol D. ; Belzberg, Allan ; Blakeley, Jaishri ; Heaphy, Christopher M. / Telomere alterations in neurofibromatosis type 1-associated solid tumors. In: Acta Neuropathologica Communications. 2019 ; Vol. 7, No. 1.
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