1. Telomere alterations in neurofibromatosis type 1-associated solid tumors
- Author
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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, and Heaphy, Christopher M
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Brain Cancer ,Cancer ,Neurofibromatosis ,Brain Disorders ,Neurosciences ,Rare Diseases ,Adult ,Brain Neoplasms ,Female ,Glioma ,Humans ,Kaplan-Meier Estimate ,Male ,Mutation ,Neurofibromatosis 1 ,Neurofibromin 1 ,Neurofibrosarcoma ,Telomere ,Telomere Homeostasis ,Young Adult ,NF1 ,ATRX ,Alternative lengthening of telomeres ,MPNST ,Biochemistry and Cell Biology ,Clinical Sciences ,Biochemistry and cell biology - 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
- Published
- 2019