TY - JOUR AU - Rodriguez, Fausto J. AU - Graham, Mindy K. AU - Brosnan-Cashman, Jacqueline A. AU - Barber, John R. AU - Davis, Christine AU - Vizcaino, M. Adelita AU - Palsgrove, Doreen N. AU - Giannini, Caterina AU - Pekmezci, Melike AU - Dahiya, Sonika AU - Gokden, Murat AU - Noë, Michael AU - Wood, Laura D. AU - Pratilas, Christine A. AU - Morris, Carol D. AU - Belzberg, Allan AU - Blakeley, Jaishri AU - Heaphy, Christopher M. PY - 2019 DA - 2019/08/28 TI - Telomere alterations in neurofibromatosis type 1-associated solid tumors JO - Acta Neuropathologica Communications SP - 139 VL - 7 IS - 1 AB - 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. SN - 2051-5960 UR - https://doi.org/10.1186/s40478-019-0792-5 DO - 10.1186/s40478-019-0792-5 ID - Rodriguez2019 ER -