Germline TERT promoter mutations are rare in familial melanomaReport as inadecuate

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Familial Cancer

, Volume 15, Issue 1, pp 139–144

First Online: 03 October 2015DOI: 10.1007-s10689-015-9841-9

Cite this article as: Harland, M., Petljak, M., Robles-Espinoza, C.D. et al. Familial Cancer 2016 15: 139. doi:10.1007-s10689-015-9841-9


Germline CDKN2A mutations occur in 40 % of 3-or-more case melanoma families while mutations of CDK4, BAP1, and genes involved in telomere function ACD, TERF2IP,POT1, have also been implicated in melanomagenesis. Mutation of the promoter of the telomerase reverse transcriptase TERT gene c.−57 T>G variant has been reported in one family. We tested for the TERT promoter variant in 675 multicase families wild-type for the known high penetrance familial melanoma genes, 1863 UK population-based melanoma cases and 529 controls. Germline lymphocyte telomere length was estimated in carriers. The c.−57 T>G TERT promoter variant was identified in one 7-case family with multiple primaries and early age of onset earliest, 15 years but not among population cases or controls. One family member had multiple primary melanomas, basal cell carcinomas and a bladder tumour. The blood leukocyte telomere length of a carrier was similar to wild-type cases. We provide evidence confirming that a rare promoter variant of TERT c.−57 T>G is associated with high penetrance, early onset melanoma and potentially other cancers, and explains <1 % of UK melanoma multicase families. The identification of POT1 and TERT germline mutations highlights the importance of telomere integrity in melanoma biology.

KeywordsMelanoma Familial Genetic TERT Mutation Julia A. Newton-Bishop, David J. Adams, D. Timothy Bishop have contributed equally to this article.

Electronic supplementary materialThe online version of this article doi:10.1007-s10689-015-9841-9 contains supplementary material, which is available to authorized users.

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Author: Mark Harland - Mia Petljak - Carla Daniela Robles-Espinoza - Zhihao Ding - Nelleke A. Gruis - Remco van Doorn - Karen A.



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