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dc.contributor.authorDalmasso, Bruna
dc.contributor.authorPastorino, Lorenza
dc.contributor.authorNathan, Vaishnavi
dc.contributor.authorShah, Nirav N.
dc.contributor.authorPalmer, Jane M.
dc.contributor.authorHowlie, Madeleine
dc.contributor.authorJohansson, Peter A.
dc.contributor.authorFreedman, Neal D.
dc.contributor.authorCarter, Brian D.
dc.contributor.authorBeane-Freeman, Laura E.
dc.contributor.authorHicks, Belynda D.
dc.contributor.authorMolven, Anders
dc.contributor.authorHelgadottir, Hildur
dc.contributor.authorSankar, Aravind
dc.contributor.authorTsao, Hensin
dc.contributor.authorStratigos, Alexander J.
dc.contributor.authorHelsing, Per
dc.contributor.authorvan Doorn, Remco
dc.contributor.authorGruis, Nelleke A.
dc.contributor.authorVisser, Mijke
dc.contributor.authorWadt, Karin Anna Wallentin
dc.contributor.authorMann, G.
dc.contributor.authorHolland, Elizabeth A.
dc.contributor.authorNagore, Eduardo
dc.contributor.authorPotrony, Miriam
dc.contributor.authorPuig, Susana
dc.contributor.authorMenin, Chiara
dc.contributor.authorPeris, Ketty
dc.contributor.authorFargnoli, Maria Concetta
dc.contributor.authorCalista, Donato
dc.contributor.authorSoufir, Nadem
dc.contributor.authorHarland, Mark
dc.contributor.authorBishop, Timmi Unger
dc.contributor.authorKanetsky, Peter A.
dc.contributor.authorElder, David E.
dc.contributor.authorAndreotti, Virginia
dc.contributor.authorVanni, Irene
dc.contributor.authorBruno, William
dc.contributor.authorHöiom, Veronica
dc.contributor.authorTucker, Margaret Anne
dc.contributor.authorYang, Xiaohong R.
dc.contributor.authorAndresen, Per Arne
dc.contributor.authorAdams, David James
dc.contributor.authorLandi, Maria Teresa
dc.contributor.authorHayward, Nicholas K.
dc.contributor.authorGoldstein, Alisa M.
dc.contributor.authorGhiorzo, Paola
dc.description.abstractPurpose Ataxia–Telangiectasia Mutated (ATM) has been implicated in the risk of several cancers, but establishing a causal relationship is often challenging. Although ATM single-nucleotide polymorphisms have been linked to melanoma, few functional alleles have been identified. Therefore, ATM impact on melanoma predisposition is unclear. Methods From 22 American, Australian, and European sites, we collected 2,104 familial, multiple primary (MPM), and sporadic melanoma cases who underwent ATM genotyping via panel, exome, or genome sequencing, and compared the allele frequency (AF) of selected ATM variants classified as loss-of-function (LOF) and variants of uncertain significance (VUS) between this cohort and the gnomAD non-Finnish European (NFE) data set. Results LOF variants were more represented in our study cohort than in gnomAD NFE, both in all (AF = 0.005 and 0.002, OR = 2.6, 95% CI = 1.56–4.11, p < 0.01), and familial + MPM cases (AF = 0.0054 and 0.002, OR = 2.97, p < 0.01). Similarly, VUS were enriched in all (AF = 0.046 and 0.033, OR = 1.41, 95% CI = 1.6–5.09, p < 0.01) and familial + MPM cases (AF = 0.053 and 0.033, OR = 1.63, p < 0.01). In a case–control comparison of two centers that provided 1,446 controls, LOF and VUS were enriched in familial + MPM cases (p = 0.027, p = 0.018). Conclusion This study, describing the largest multicenter melanoma cohort investigated for ATM germline variants, supports the role of ATM as a melanoma predisposition gene, with LOF variants suggesting a moderate-risk.en_US
dc.rightsNavngivelse 4.0 Internasjonal*
dc.titleGermline ATM variants predispose to melanoma: a joint analysis across the GenoMEL and MelaNostrum consortiaen_US
dc.typeJournal articleen_US
dc.typePeer revieweden_US
dc.rights.holderCopyright The Author(s) 2021en_US
dc.source.journalGenetics in Medicineen_US
dc.identifier.citationGenetics in Medicine. 2021, 23 (11), 2087-2095.en_US

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Navngivelse 4.0 Internasjonal
Except where otherwise noted, this item's license is described as Navngivelse 4.0 Internasjonal