학술논문
Telomere alterations in neurofibromatosis type 1-associated solid tumors
Document Type
article
Author
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
Source
Acta Neuropathologica Communications, Vol 7, Iss 1, Pp 1-11 (2019)
Subject
Language
English
ISSN
2051-5960
Abstract
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