{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T15:51:33Z","timestamp":1764172293033},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2018,5,1]],"date-time":"2018-05-01T00:00:00Z","timestamp":1525132800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Risk of melanoma is in part determined by genetic factors. Currently the only established high penetrance familial melanoma genes are CDKN2A and CDK4. Recent studies reported germline variants in POT1 in melanoma families. In the present study, we sequenced the entire POT1 gene in 694 patients from the M3-study. Patients with multiple primary melanomas (n = 163) or with a positive family history (n = 133) were classified as high-risk melanoma patients. Additionally, 200 single primary melanoma patients and 198 non-melanoma controls were sequenced. For prediction analysis 10 different tools were used.<\/jats:p>\n               <jats:p>In total 53 different variants were found, of which 8 were detected in high-risk melanoma patients, only. Two out of these 8 variants were located in exons and were non-synonymous: g.124510982 G&amp;gt;A (p.R80C) and g.124491977 T&amp;gt;G (p.N300H). While g.124491977 T&amp;gt;G was predicted to be neutral, 80% of the prediction tools classified g.124510982 G&amp;gt;A as deleterious. The variant, g.124467236 T&amp;gt;C, which possibly causes a change in the splice site was identified in a case with a positive family history in the present study. Another variant in the 5-UTR, g.124537261 A&amp;gt;G, was found in 2 high-risk patients. So, in conclusion, melanoma associated POT1 germline variants seem to be rare. Further studies are required to evaluate the role of POT1 for genetic counseling.<\/jats:p>","DOI":"10.1534\/g3.117.300394","type":"journal-article","created":{"date-parts":[[2018,3,10]],"date-time":"2018-03-10T01:55:22Z","timestamp":1520646922000},"page":"1475-1480","source":"Crossref","is-referenced-by-count":18,"title":["Germline Variants in the POT1-Gene in High-Risk Melanoma Patients in Austria"],"prefix":"10.1093","volume":"8","author":[{"given":"Christoph","family":"M\u00fcller","sequence":"first","affiliation":[{"name":"Department of Dermatology, Medical University of Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milica","family":"Krunic","sequence":"additional","affiliation":[{"name":"Center for Integrative Bioinformatics Vienna, Max F. Perutz Laboratories, University of Vienna, Medical University Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judith","family":"Wendt","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Medical University of Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arndt","family":"von Haeseler","sequence":"additional","affiliation":[{"name":"Center for Integrative Bioinformatics Vienna, Max F. Perutz Laboratories, University of Vienna, Medical University Vienna, Austria"},{"name":"Bioinformatics and Computational Biology, Faculty of Computer Science, University of Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ichiro","family":"Okamoto","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Medical University of Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2018,5,1]]},"reference":[{"issue":"4","key":"2021041814352451000_bib1","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1038\/nmeth0410-248","article-title":"A method and server for predicting damaging missense mutations.","volume":"7","author":"Adzhubei","year":"2010","journal-title":"Nat. Methods"},{"key":"2021041814352451000_bib2","doi-asserted-by":"publisher","first-page":"dju408","DOI":"10.1093\/jnci\/dju408","article-title":"Nonsense mutations in the shelterin complex genes ACD and TERF2IP in familial melanoma.","volume":"107","author":"Aoude","year":"2015","journal-title":"J. Natl. Cancer Inst."},{"issue":"1","key":"2021041814352451000_bib3","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1093\/jnci\/dju384","article-title":"Germline mutations in shelterin complex genes are associated with familial glioma.","volume":"107","author":"Bainbridge","year":"2015","journal-title":"J. Natl. Cancer Inst."},{"issue":"11","key":"2021041814352451000_bib4","doi-asserted-by":"publisher","first-page":"3823","DOI":"10.1093\/nar\/gkm238","article-title":"SNAP: predict effect of non-synonymous polymorphisms on function.","volume":"35","author":"Bromberg","year":"2007","journal-title":"Nucleic Acids Res."},{"issue":"5","key":"2021041814352451000_bib5","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1097\/CMR.0000000000000179","article-title":"Novel CDKN2A mutations in Austrian melanoma patients.","volume":"25","author":"Burgstaller-Muehlbacher","year":"2015","journal-title":"Melanoma Res."},{"issue":"1","key":"2021041814352451000_bib6","doi-asserted-by":"publisher","first-page":"8383","DOI":"10.1038\/ncomms9383","article-title":"A mutation in the POT1 gene is responsible for cardiac angiosarcoma in TP53-negative Li-Fraumeni-like families.","volume":"6","author":"Calvete","year":"2015","journal-title":"Nat. Commun."},{"issue":"10","key":"2021041814352451000_bib7","doi-asserted-by":"publisher","first-page":"e46688","DOI":"10.1371\/journal.pone.0046688","article-title":"Predicting the functional effect of amino acid substitutions and indels.","volume":"7","author":"Choi","year":"2012","journal-title":"PLoS One"},{"key":"2021041814352451000_bib8","doi-asserted-by":"publisher","first-page":"11883","DOI":"10.1038\/ncomms11883","article-title":"Rare disruptive mutations and their contribution to the heritable risk of colorectal cancer.","volume":"7","author":"Chubb","year":"2016","journal-title":"Nat. Commun."},{"issue":"12","key":"2021041814352451000_bib9","doi-asserted-by":"publisher","first-page":"e1001025","DOI":"10.1371\/journal.pcbi.1001025","article-title":"Identifying a high fraction of the human genome to be under selective constraint using GERP++.","volume":"6","author":"Davydov","year":"2010","journal-title":"PLOS Comput. Biol."},{"issue":"2","key":"2021041814352451000_bib10","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1136\/jmg.2006.043802","article-title":"Features associated with germline CDKN2A mutations: a GenoMEL study of melanoma-prone families from three continents.","volume":"44","author":"Goldstein","year":"2007","journal-title":"J. Med. Genet."},{"issue":"12","key":"2021041814352451000_bib11","doi-asserted-by":"publisher","first-page":"2655","DOI":"10.1002\/ijc.30288","article-title":"Telomere structure and maintenance gene variants and risk of five cancer types.","volume":"139","author":"Karami","year":"2016","journal-title":"Int. J. Cancer"},{"issue":"3","key":"2021041814352451000_bib12","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1038\/ng.2892","article-title":"A general framework for estimating the relative pathogenicity of human genetic variants.","volume":"46","author":"Kircher","year":"2014","journal-title":"Nat. Genet."},{"issue":"16","key":"2021041814352451000_bib13","doi-asserted-by":"publisher","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","article-title":"The Sequence Alignment\/Map format and SAMtools.","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"issue":"9","key":"2021041814352451000_bib14","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.1101\/gr.107524.110","article-title":"The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data.","volume":"20","author":"McKenna","year":"2010","journal-title":"Genome Res."},{"key":"2021041814352451000_bib15","doi-asserted-by":"publisher","first-page":"D377","DOI":"10.1093\/nar\/gks1118","article-title":"PANTHER in 2013: modeling the evolution of gene function, and other gene attributes, in the context of phylogenetic trees.","volume":"41","author":"Mi","year":"2013","journal-title":"Nucleic Acids Res."},{"issue":"6","key":"2021041814352451000_bib16","doi-asserted-by":"publisher","first-page":"1308","DOI":"10.1111\/bjd.14407","article-title":"Characterization of patients at high risk of melanoma in Austria.","volume":"174","author":"M\u00fcller","year":"2016","journal-title":"Br. J. Dermatol."},{"issue":"5","key":"2021041814352451000_bib17","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1101\/gr.176601","article-title":"Predicting deleterious amino acid substitutions.","volume":"11","author":"Ng","year":"2001","journal-title":"Genome Res."},{"issue":"1","key":"2021041814352451000_bib18","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1101\/gr.097857.109","article-title":"Detection of nonneutral substitution rates on mammalian phylogenies.","volume":"20","author":"Pollard","year":"2010","journal-title":"Genome Res."},{"issue":"5","key":"2021041814352451000_bib19","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1038\/ng.2947","article-title":"POT1 loss-of-function variants predispose to familial melanoma.","volume":"46","author":"Robles-Espinoza","year":"2014","journal-title":"Nat. Genet."},{"issue":"4","key":"2021041814352451000_bib20","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1038\/nmeth.2890","article-title":"MutationTaster2: mutation prediction for the deep-sequencing age.","volume":"11","author":"Schwarz","year":"2014","journal-title":"Nat. Methods"},{"issue":"21","key":"2021041814352451000_bib21","doi-asserted-by":"publisher","first-page":"2790","DOI":"10.1093\/bioinformatics\/btt468","article-title":"NextGenMap: fast and accurate read mapping in highly polymorphic genomes.","volume":"29","author":"Sedlazeck","year":"2013","journal-title":"Bioinformatics"},{"issue":"1","key":"2021041814352451000_bib22","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1093\/nar\/29.1.308","article-title":"dbSNP: the NCBI database of genetic variation.","volume":"29","author":"Sherry","year":"2001","journal-title":"Nucleic Acids Res."},{"issue":"5","key":"2021041814352451000_bib23","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1038\/ng.2941","article-title":"Rare missense variants in POT1 predispose to familial cutaneous malignant melanoma.","volume":"46","author":"Shi","year":"2014","journal-title":"Nat. Genet."},{"issue":"19","key":"2021041814352451000_bib24","doi-asserted-by":"publisher","first-page":"2319","DOI":"10.1182\/blood-2016-01-695692","article-title":"Germline mutations in shelterin complex genes are associated with familial chronic lymphocytic leukemia.","volume":"128","author":"Speedy","year":"2016","journal-title":"Blood"},{"issue":"1","key":"2021041814352451000_bib25","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1186\/1471-2105-11-548","article-title":"Protein structure analysis of mutations causing inheritable diseases. An e-Science approach with life scientist friendly interfaces.","volume":"11","author":"Venselaar","year":"2010","journal-title":"BMC Bioinformatics"},{"key":"2021041814352451000_bib26","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1007\/s10689-017-9984-y","volume":"16","author":"Wilson","year":"2017"},{"issue":"1","key":"2021041814352451000_bib27","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1038\/ng0196-97","article-title":"Germline mutations in the p16INK4a binding domain of CDK4 in familial melanoma.","volume":"12","author":"Zuo","year":"1996","journal-title":"Nat. Genet."}],"container-title":["G3 Genes|Genomes|Genetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/g3journal\/article-pdf\/8\/5\/1475\/37126524\/g3journal1475.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/g3journal\/article-pdf\/8\/5\/1475\/37126524\/g3journal1475.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,18]],"date-time":"2021-04-18T14:35:33Z","timestamp":1618756533000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/g3journal\/article\/8\/5\/1475\/6028147"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,5,1]]},"references-count":27,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2018,5,1]]}},"URL":"https:\/\/doi.org\/10.1534\/g3.117.300394","relation":{},"ISSN":["2160-1836"],"issn-type":[{"value":"2160-1836","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2018,5,1]]},"published":{"date-parts":[[2018,5,1]]}}}