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Lookup NU author(s): Professor Neil RajanORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© Author(s) (or their employer(s)) 2025. Constitutional or germline pathogenic variants (GPVs) in protection of telomeres 1 (POT1) are associated with a variety of tumours resulting in the recognition of POT1-tumour predisposition syndrome (POT1-TPDS). These tumours may include cutaneous melanoma, angiosarcoma, haematological malignancy and brain tumours. Due to the rarity of POT1 GPVs and limited available data, the overall lifetime cancer risks for individuals with POT1-TPDS are unclear. Furthermore, there is scant evidence to support the role of surveillance in early cancer detection in this patient group. A recent international publication suggested a surveillance protocol similar to that used in Li-Fraumeni Syndrome (LFS) could be offered to POT1 pathogenic variant carriers, particularly where there are LFS-like features. However, current evidence for POT1-TPDS is not supportive of an equivalent lifetime cancer risk. Given the inclusion of POT1 in the National Test Directory in England and the need for UK-based guidance, an expert group undertook a literature review to assess the phenotypic spectrum of POT1-TPDS and to provide lifetime risk estimates of POT1-associated cancers. The available evidence was shared with a small working group of experts that included clinical geneticists, dermatologists, sarcoma specialists, haematologists and radiologists to cover all aspects of the cancers most commonly associated with POT1-TPDS. Following structured expert group discussions, we achieved consensus on best practice recommendations for a POT1-TPDS UK management protocol.
Author(s): Tsoulaki O, Evans DG, Sinha K, Rajan N, Bakr F, Hatcher H, Napolitano A, Finn E, Iyengar S, Sohaib A, Sadler TJ, Forde C, Woodward ER, McVeigh TP, Tischkowitz M, Lalloo F, Hanson H
Publication type: Article
Publication status: Published
Journal: Journal of Medical Genetics
Year: 2025
Volume: 62
Issue: 9
Pages: 559-565
Online publication date: 11/05/2025
Acceptance date: 25/03/2025
Date deposited: 28/05/2025
ISSN (print): 0022-2593
ISSN (electronic): 1468-6244
Publisher: BMJ Publishing Group
URL: https://doi.org/10.1136/jmg-2025-110638
DOI: 10.1136/jmg-2025-110638
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