TY - JOUR
T1 - Telomere alterations in neurofibromatosis type 1-associated solid tumors
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.
N1 - Funding Information:
This work was supported in part by Pilocytic/Pilomyxoid Fund, including Lauren’s First and Goal, and the Stick it to Brain Tumors Annual Women’s Ice Hockey Tournament (FJR), the Basic/Translational Science Investigator Award from the North American Neuroendocrine Tumor Society supported by the Neuroendocrine Tumor Research Foundation (CMH), a collaborative grant between the Wilmer Eye Institute (Baltimore, MD) and the King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia (to FJR), Department of Defense grant W81XWH-18-1-0496 (FJR), NIH grant 2T32CA009110-39A1 (JAB), and NIH grant P30 CA006973 to the Sidney Kimmel Comprehensive Cancer Center (PI: W. Nelson).
PY - 2019/8/28
Y1 - 2019/8/28
N2 - 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.
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.
KW - ATRX
KW - Alternative lengthening of telomeres
KW - Glioma
KW - MPNST
KW - NF1
UR - https://www.scopus.com/pages/publications/85071630752
U2 - 10.1186/s40478-019-0792-5
DO - 10.1186/s40478-019-0792-5
M3 - Article
C2 - 31462295
AN - SCOPUS:85071630752
SN - 2051-5960
VL - 7
SP - 139
JO - Acta Neuropathologica Communications
JF - Acta Neuropathologica Communications
IS - 1
ER -