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dc.contributor.authorHarland, Marken
dc.contributor.authorPetljak, Miaen
dc.contributor.authorRobles-Espinoza, Carla Danielaen
dc.contributor.authorDing, Zhihaoen
dc.contributor.authorGruis, Nelleke Aen
dc.contributor.authorvan, Doorn Remcoen
dc.contributor.authorPooley, Karenen
dc.contributor.authorDunning, Alisonen
dc.contributor.authorAoude, Lauren Gen
dc.contributor.authorWadt, Karin AWen
dc.contributor.authorGerdes, Anne-Marieen
dc.contributor.authorBrown, Kevin Men
dc.contributor.authorHayward, Nicholas Ken
dc.contributor.authorNewton-Bishop, Julia Aen
dc.contributor.authorAdams, David Jen
dc.contributor.authorBishop, D Timothyen
dc.date.accessioned2015-10-07T09:40:15Z
dc.date.available2015-10-07T09:40:15Z
dc.date.issued2015-10-03en
dc.identifier.citationFamilial Cancer 2016, 15(1): 139-144. doi:10.1007/s10689-015-9841-9en
dc.identifier.issn1389-9600
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/251341
dc.description.abstractGermline 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.
dc.description.sponsorshipThe authors would like to thank the families for their willingness to participate; and Rajiv Kumar for the provision of mutation positive samples. The collection of samples in the UK population-ascertained sample set was funded by Cancer Research UK (awards C588/A19167 and C8216/A6129) and by the NIH (CA83115). The work of N.A.G. and R.v.D was supported by the Dutch Cancer Society (UL 2012-5489). D.J.A and C.D.R.E are supported by Cancer Research UK, ERC Combat Cancer and the Wellcome Trust. N.K.H is supported by a fellowship from the National Health and Medical Research Council of Australia. A.M.D. and K.A.P. were supported by CRUK grant (C8197/A16565) and The Isaac Newton Trust. K.M.B. is supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics; National Cancer Institute; National Institutes of Health.
dc.languageEnglishen
dc.language.isoenen
dc.publisherSpringer
dc.rightsAttribution 2.0 UK: England & Wales*
dc.rights.urihttp://creativecommons.org/licenses/by/2.0/uk/*
dc.subjectMelanomaen
dc.subjectFamilialen
dc.subjectGeneticen
dc.subjectTERTen
dc.subjectMutationen
dc.titleGermline TERT promoter mutations are rare in familial melanomaen
dc.typeArticle
dc.description.versionThis is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s10689-015-9841-9en
prism.endingPage144
prism.publicationDate2015en
prism.publicationNameFamilial Canceren
prism.startingPage139
prism.volume15en
dc.rioxxterms.funderCRUK
dc.rioxxterms.funderNIH
dc.rioxxterms.funderERC
dc.rioxxterms.funderWellcome Trust
dc.rioxxterms.projectidC588/A19167
dc.rioxxterms.projectidC8216/A6129
dc.rioxxterms.projectidCA83115
dc.rioxxterms.projectidC8197/A16565
rioxxterms.versionofrecord10.1007/s10689-015-9841-9en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2015-10-03en
dc.contributor.orcidPooley, Karen [0000-0002-1274-9460]
dc.contributor.orcidDunning, Alison [0000-0001-6651-7166]
dc.identifier.eissn1573-7292
rioxxterms.typeJournal Article/Reviewen


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Attribution 2.0 UK: England & Wales
Except where otherwise noted, this item's licence is described as Attribution 2.0 UK: England & Wales