Telomere alterations in neurofibromatosis type 1-associated solid tumors | Acta Neuropathologica Communications | Full Text

Telomere alterations in neurofibromatosis type 1-associated solid tumors | Acta Neuropathologica Communications | Full Text



Acta Neuropathologica Communications

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 

Acta Neuropathologica Communicationsvolume 7, Article number: 139 (2019) | Download Citation

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.