Telomere erosion in NF1 tumorigenesis

Robinson, Rhiannon, Grimstead, Julia, Sedani, Ashni, Baird, Duncan ORCID: https://orcid.org/0000-0001-8408-5467 and Upadhyaya, Meena 2017. Telomere erosion in NF1 tumorigenesis. Oncotarget 8 (25) , pp. 40132-40139. 10.18632/oncotarget.16981

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Abstract

Neurofibromatosis type 1 (NF1; MIM# 162200) is a familial cancer syndrome that affects 1 in 3,500 individuals worldwide and is inherited in an autosomal dominant fashion. Malignant Peripheral Nerve Sheath Tumors (MPNSTs) represent a significant cause of morbidity and mortality in NF1 and currently there is no treatment or definite prognostic biomarkers for these tumors. Telomere shortening has been documented in numerous tumor types. Short dysfunctional telomeres are capable of fusion and it is considered that the ensuing genomic instability may facilitate clonal evolution and the progression to malignancy. To evaluate the potential role of telomere dysfunction in NF1-associated tumors, we undertook a comparative analysis of telomere length in samples derived from 10 cutaneous and 10 diffused plexiform neurofibromas, and 19 MPNSTs. Telomere length was determined using high-resolution Single Telomere Length Analysis (STELA). The mean Xp/Yp telomere length detected in MPNSTs, at 3.282 kb, was significantly shorter than that observed in both plexiform neurofibromas (5.793 kb; [p = 0.0006]) and cutaneous neurofibromas (6.141 kb; [p = 0.0007]). The telomere length distributions of MPNSTs were within the length-ranges in which telomere fusion is detected and that confer a poor prognosis in other tumor types. These data indicate that telomere length may play a role in driving genomic instability and clonal progression in NF1-associated MPNSTs.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > R Medicine (General)
Uncontrolled Keywords:	Telomere, NF1, MPNST, genetic instability, cancer
Publisher:	Impact Journals
ISSN:	1949-2553
Funders:	Cancer Research UK
Date of First Compliant Deposit:	26 May 2017
Date of Acceptance:	2 March 2017
Last Modified:	06 May 2023 03:38
URI:	https://orca.cardiff.ac.uk/id/eprint/99113

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