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.
Original language | English (US) |
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Pages (from-to) | 139 |
Number of pages | 1 |
Journal | Acta Neuropathologica Communications |
Volume | 7 |
Issue number | 1 |
DOIs | |
State | Published - Aug 28 2019 |
Funding
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).
Keywords
- ATRX
- Alternative lengthening of telomeres
- Glioma
- MPNST
- NF1
ASJC Scopus subject areas
- Pathology and Forensic Medicine
- Clinical Neurology
- Cellular and Molecular Neuroscience