{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T20:46:26Z","timestamp":1790023586000,"version":"4.0.1"},"reference-count":62,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2018,4,11]],"date-time":"2018-04-11T00:00:00Z","timestamp":1523404800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1026112"],"award-info":[{"award-number":["APP1026112"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1093017"],"award-info":[{"award-number":["APP1093017"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Jack and Rae Cowie"},{"name":"Townsville Central Rotary Club"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0194098","type":"journal-article","created":{"date-parts":[[2018,4,11]],"date-time":"2018-04-11T18:05:10Z","timestamp":1523469910000},"page":"e0194098","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":23,"title":["Germline mutations in candidate predisposition genes in individuals with cutaneous melanoma and at least two independent additional primary cancers"],"prefix":"10.1371","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5336-0454","authenticated-orcid":true,"given":"Antonia L.","family":"Pritchard","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter A.","family":"Johansson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vaishnavi","family":"Nathan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeleine","family":"Howlie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Symmons","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane M.","family":"Palmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas K.","family":"Hayward","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2018,4,11]]},"reference":[{"issue":"1","key":"ref1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1136\/jmedgenet-2015-103150","article-title":"Melanoma genetics","volume":"53","author":"J Read","year":"2016","journal-title":"J Med Genet"},{"issue":"2","key":"ref2","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1111\/pcmr.12333","article-title":"Genetics of familial melanoma: 20 years after CDKN2A","volume":"28","author":"LG Aoude","year":"2015","journal-title":"Pigment Cell Melanoma Res"},{"issue":"9","key":"ref3","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1038\/ng.3373","article-title":"Genome-wide meta-analysis identifies five new susceptibility loci for cutaneous malignant melanoma","volume":"47","author":"MH Law","year":"2015","journal-title":"Nat Genet"},{"issue":"7","key":"ref4","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1016\/j.cell.2015.05.044","article-title":"Genomic Classification of Cutaneous Melanoma","volume":"161","author":"N Cancer Genome Atlas","year":"2015","journal-title":"Cell"},{"issue":"2","key":"ref5","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1002\/cncr.29041","article-title":"Cancers associated with BRCA1 and BRCA2 mutations other than breast and ovarian","volume":"121","author":"J Mersch","year":"2015","journal-title":"Cancer"},{"issue":"4","key":"ref6","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1007\/s10689-007-9143-y","article-title":"BRCA1, BRCA2, TP53, and CDKN2A germline mutations in patients with breast cancer and cutaneous melanoma","volume":"6","author":"C Monnerat","year":"2007","journal-title":"Familial cancer"},{"issue":"24","key":"ref7","doi-asserted-by":"crossref","first-page":"2336","DOI":"10.1056\/NEJMoa1508054","article-title":"Germline Mutations in Predisposition Genes in Pediatric Cancer","volume":"373","author":"J Zhang","year":"2015","journal-title":"N Engl J Med"},{"issue":"4","key":"ref8","doi-asserted-by":"crossref","first-page":"e94554","DOI":"10.1371\/journal.pone.0094554","article-title":"Germline variation in cancer-susceptibility genes in a healthy, ancestrally diverse cohort: implications for individual genome sequencing","volume":"9","author":"DL Bodian","year":"2014","journal-title":"PLoS One"},{"issue":"8","key":"ref9","doi-asserted-by":"crossref","first-page":"e72144","DOI":"10.1371\/journal.pone.0072144","article-title":"A BAP1 mutation in a Danish family predisposes to uveal melanoma and other cancers","volume":"8","author":"LG Aoude","year":"2013","journal-title":"PLoS One"},{"issue":"2","key":"ref10","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1375\/twin.11.2.183","article-title":"The Queensland Study of Melanoma: environmental and genetic associations (Q-MEGA); study design, baseline characteristics, and repeatability of phenotype and sun exposure measures","volume":"11","author":"AJ Baxter","year":"2008","journal-title":"Twin Res Hum Genet"},{"issue":"5","key":"ref11","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1093\/jnci\/91.5.446","article-title":"CDKN2A variants in a population-based sample of Queensland families with melanoma","volume":"91","author":"J Aitken","year":"1999","journal-title":"J Natl Cancer Inst"},{"issue":"14","key":"ref12","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","article-title":"Fast and accurate short read alignment with Burrows-Wheeler transform","volume":"25","author":"H Li","year":"2009","journal-title":"Bioinformatics"},{"issue":"16","key":"ref13","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","article-title":"The Sequence Alignment\/Map format and SAMtools","volume":"25","author":"H Li","year":"2009","journal-title":"Bioinformatics"},{"issue":"21","key":"ref14","doi-asserted-by":"crossref","first-page":"2865","DOI":"10.1093\/bioinformatics\/btp394","article-title":"Pindel: a pattern growth approach to detect break points of large deletions and medium sized insertions from paired-end short reads","volume":"25","author":"K Ye","year":"2009","journal-title":"Bioinformatics"},{"issue":"16","key":"ref15","doi-asserted-by":"crossref","first-page":"e164","DOI":"10.1093\/nar\/gkq603","article-title":"ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data","volume":"38","author":"K Wang","year":"2010","journal-title":"Nucleic Acids Res"},{"issue":"22","key":"ref16","doi-asserted-by":"crossref","first-page":"3216","DOI":"10.1093\/bioinformatics\/btr540","article-title":"Kaviar: an accessible system for testing SNV novelty","volume":"27","author":"G Glusman","year":"2011","journal-title":"Bioinformatics"},{"issue":"7","key":"ref17","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/gim.2013.73","article-title":"ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. Genetics in medicine: official journal of the","volume":"15","author":"RC Green","year":"2013","journal-title":"American College of Medical Genetics"},{"key":"ref18","unstructured":"McKusick-Nathans Institute of Genetic Medicine JHUB, MD). Online Mendelian Inheritance in Man, OMIM\u00ae 2016 [cited 2016]. Available from: <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/omim.org\/\" xlink:type=\"simple\">http:\/\/omim.org\/<\/ext-link>."},{"issue":"5","key":"ref19","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1002\/humu.21438","article-title":"LOVD v.2.0: the next generation in gene variant databases","volume":"32","author":"IF Fokkema","year":"2011","journal-title":"Human mutation"},{"issue":"5","key":"ref20","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1038\/ng.2947","article-title":"POT1 loss-of-function variants predispose to familial melanoma","volume":"46","author":"CD Robles-Espinoza","year":"2014","journal-title":"Nat Genet"},{"issue":"2","key":"ref21","doi-asserted-by":"crossref","DOI":"10.1093\/jnci\/dju408","article-title":"Nonsense mutations in the shelterin complex genes ACD and TERF2IP in familial melanoma","volume":"107","author":"LG Aoude","year":"2015","journal-title":"J Natl Cancer Inst"},{"issue":"7375","key":"ref22","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/nature10630","article-title":"A novel recurrent mutation in MITF predisposes to familial and sporadic melanoma","volume":"480","author":"S Yokoyama","year":"2011","journal-title":"Nature"},{"key":"ref23","article-title":"Inherited DNA-Repair Gene Mutations in Men with Metastatic Prostate Cancer","author":"CC Pritchard","year":"2016","journal-title":"N Engl J Med"},{"issue":"7","key":"ref24","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1038\/nprot.2009.86","article-title":"Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm","volume":"4","author":"P Kumar","year":"2009","journal-title":"Nat Protoc"},{"key":"ref25","doi-asserted-by":"crossref","DOI":"10.1002\/0471142905.hg0720s76","article-title":"Predicting functional effect of human missense mutations using PolyPhen-2","author":"I Adzhubei","year":"2013","journal-title":"Curr Protoc Hum Genet"},{"issue":"9","key":"ref26","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1101\/gr.092619.109","article-title":"Identification of deleterious mutations within three human genomes","volume":"19","author":"S Chun","year":"2009","journal-title":"Genome research"},{"issue":"8","key":"ref27","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1038\/nmeth0810-575","article-title":"MutationTaster evaluates disease-causing potential of sequence alterations","volume":"7","author":"JM Schwarz","year":"2010","journal-title":"Nat Methods"},{"issue":"3","key":"ref28","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1002\/humu.20210","article-title":"UMD (Universal Mutation Database): 2005 update","volume":"26","author":"C Beroud","year":"2005","journal-title":"Human mutation"},{"issue":"9","key":"ref29","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1002\/humu.23035","article-title":"TP53 Variations in Human Cancers: New Lessons from the IARC TP53 Database and Genomics Data","volume":"37","author":"L Bouaoun","year":"2016","journal-title":"Human mutation"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"D339","DOI":"10.1093\/nar\/gkm700","article-title":"The telomerase database","volume":"36","author":"JD Podlevsky","year":"2008","journal-title":"Nucleic Acids Res"},{"issue":"4","key":"ref31","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1002\/humu.20928","article-title":"Multiple endocrine neoplasia type 2 RET protooncogene database: repository of MEN2-associated RET sequence variation and reference for genotype\/phenotype correlations","volume":"30","author":"RL Margraf","year":"2009","journal-title":"Human mutation"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"D945","DOI":"10.1093\/nar\/gkq929","article-title":"COSMIC: mining complete cancer genomes in the Catalogue of Somatic Mutations in Cancer","volume":"39","author":"SA Forbes","year":"2011","journal-title":"Nucleic Acids Res"},{"issue":"5","key":"ref33","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1158\/2159-8290.CD-12-0095","article-title":"The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data","volume":"2","author":"E Cerami","year":"2012","journal-title":"Cancer Discov"},{"issue":"4","key":"ref34","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1038\/35067100","article-title":"Cbl: many adaptations to regulate protein tyrosine kinases","volume":"2","author":"CB Thien","year":"2001","journal-title":"Nature reviews Molecular cell biology"},{"issue":"8","key":"ref35","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1002\/humu.22809","article-title":"Molecular Diversity and Associated Phenotypic Spectrum of Germline CBL Mutations","volume":"36","author":"S Martinelli","year":"2015","journal-title":"Human mutation"},{"issue":"4","key":"ref36","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1002\/humu.42","article-title":"A rare variant, I852M, of the RET proto-oncogene in a patient with medullary thyroid carcinoma at age 20 years","volume":"17","author":"R Demeester","year":"2001","journal-title":"Human mutation"},{"issue":"1","key":"ref37","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3324\/haematol.2008.001271","article-title":"Clinical relevance of JAK2 (V617F) mutant allele burden","volume":"94","author":"F Passamonti","year":"2009","journal-title":"Haematologica"},{"issue":"4","key":"ref38","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1038\/ng.342","article-title":"A germline JAK2 SNP is associated with predisposition to the development of JAK2(V617F)-positive myeloproliferative neoplasms","volume":"41","author":"O Kilpivaara","year":"2009","journal-title":"Nat Genet"},{"issue":"2","key":"ref39","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1038\/ng1001-189","article-title":"The gene mutated in ataxia-ocular apraxia 1 encodes the new HIT\/Zn-finger protein aprataxin","volume":"29","author":"MC Moreira","year":"2001","journal-title":"Nat Genet"},{"issue":"3","key":"ref40","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/0092-8674(92)90450-Q","article-title":"Mutations in the DNA ligase I gene of an individual with immunodeficiencies and cellular hypersensitivity to DNA-damaging agents","volume":"69","author":"DE Barnes","year":"1992","journal-title":"Cell"},{"issue":"2","key":"ref41","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1001\/archdermatol.2010.428","article-title":"Multiple primary cutaneous melanomas in Li-Fraumeni syndrome","volume":"147","author":"C Curiel-Lewandrowski","year":"2011","journal-title":"Arch Dermatol"},{"issue":"Suppl 6","key":"ref42","doi-asserted-by":"crossref","first-page":"vi31","DOI":"10.1093\/annonc\/mdr373","article-title":"BRCA in breast cancer: ESMO Clinical Practice Guidelines","volume":"22","author":"J Balmana","year":"2011","journal-title":"Ann Oncol"},{"issue":"3","key":"ref43","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1038\/ng1197-271","article-title":"Germline mutation of MSH6 as the cause of hereditary nonpolyposis colorectal cancer","volume":"17","author":"M Miyaki","year":"1997","journal-title":"Nat Genet"},{"issue":"2","key":"ref44","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1038\/13773","article-title":"Familial endometrial cancer in female carriers of MSH6 germline mutations","volume":"23","author":"J Wijnen","year":"1999","journal-title":"Nat Genet"},{"issue":"3","key":"ref45","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1093\/jnci\/djp473","article-title":"Risks of Lynch syndrome cancers for MSH6 mutation carriers","volume":"102","author":"L Baglietto","year":"2010","journal-title":"J Natl Cancer Inst"},{"issue":"8","key":"ref46","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1016\/j.celrep.2015.02.005","article-title":"Leukemia-associated somatic mutations drive distinct patterns of age-related clonal hemopoiesis","volume":"10","author":"T McKerrell","year":"2015","journal-title":"Cell Rep"},{"issue":"11","key":"ref47","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1038\/ng1449","article-title":"Constitutional aneuploidy and cancer predisposition caused by biallelic mutations in BUB1B","volume":"36","author":"S Hanks","year":"2004","journal-title":"Nat Genet"},{"issue":"8","key":"ref48","doi-asserted-by":"crossref","first-page":"e6554","DOI":"10.1371\/journal.pone.0006554","article-title":"Genome-wide profile of pleural mesothelioma versus parietal and visceral pleura: the emerging gene portrait of the mesothelioma phenotype","volume":"4","author":"OD Roe","year":"2009","journal-title":"PLoS One"},{"issue":"2","key":"ref49","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/S0304-3835(00)00340-2","article-title":"Mutation and expression analysis of human BUB1 and BUB1B in aneuploid breast cancer cell lines","volume":"152","author":"KA Myrie","year":"2000","journal-title":"Cancer Lett"},{"issue":"9","key":"ref50","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1002\/cncr.27967","article-title":"Identification of ROS1 rearrangement in gastric adenocarcinoma","volume":"119","author":"J Lee","year":"2013","journal-title":"Cancer"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"3116","DOI":"10.1038\/ncomms4116","article-title":"Kinase fusions are frequent in Spitz tumours and spitzoid melanomas","volume":"5","author":"T Wiesner","year":"2014","journal-title":"Nat Commun"},{"key":"ref52","article-title":"Acral Lentiginous Melanoma Harboring a ROS1 Gene Fusion With Clinical Response to Entrectinib","author":"KL Couts","year":"2017","journal-title":"Precision Oncology"},{"issue":"4","key":"ref53","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1086\/491674","article-title":"Identification of four gene variants associated with myocardial infarction","volume":"77","author":"D Shiffman","year":"2005","journal-title":"Am J Hum Genet"},{"issue":"2","key":"ref54","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1002\/ijc.29396","article-title":"Frequency and phenotypic spectrum of germline mutations in POLE and seven other polymerase genes in 266 patients with colorectal adenomas and carcinomas","volume":"137","author":"I Spier","year":"2015","journal-title":"Int J Cancer"},{"key":"ref55","doi-asserted-by":"crossref","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":"D Chubb","year":"2016","journal-title":"Nat Commun"},{"issue":"4","key":"ref56","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1007\/s10689-015-9826-8","article-title":"POLE mutations in families predisposed to cutaneous melanoma","volume":"14","author":"LG Aoude","year":"2015","journal-title":"Familial cancer"},{"issue":"5","key":"ref57","doi-asserted-by":"crossref","first-page":"e1004725","DOI":"10.1371\/journal.pcbi.1004725","article-title":"Towards Increasing the Clinical Relevance of In Silico Methods to Predict Pathogenic Missense Variants","volume":"12","author":"DL Masica","year":"2016","journal-title":"PLoS Comput Biol"},{"issue":"6","key":"ref58","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1111\/pcmr.12006","article-title":"A cryptic BAP1 splice mutation in a family with uveal and cutaneous melanoma, and paraganglioma","volume":"25","author":"K Wadt","year":"2012","journal-title":"Pigment Cell Melanoma Res"},{"key":"ref59","article-title":"A recurrent germline BAP1 mutation and extension of the BAP1 tumor predisposition spectrum to include basal cell carcinoma","author":"KA Wadt","year":"2014","journal-title":"Clinical genetics"},{"issue":"2","key":"ref60","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1167\/iovs.02-0026","article-title":"Contribution of germline mutations in BRCA2, P16(INK4A), P14(ARF) and P15 to uveal melanoma","volume":"44","author":"N Hearle","year":"2003","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"7","key":"ref61","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1001\/jama.1995.03520310033026","article-title":"A collaborative survey of 80 mutations in the BRCA1 breast and ovarian cancer susceptibility gene. Implications for presymptomatic testing and screening","volume":"273","author":"D Shattuck-Eidens","year":"1995","journal-title":"JAMA"},{"issue":"1","key":"ref62","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1086\/513891","article-title":"Cancer risks in two large breast cancer families linked to BRCA2 on chromosome 13q12-13","volume":"61","author":"DF Easton","year":"1997","journal-title":"Am J Hum Genet"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0194098","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,10,31]],"date-time":"2020-10-31T14:58:26Z","timestamp":1604156306000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0194098"}},"subtitle":[],"editor":[{"given":"Nikolas K.","family":"Haass","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2018,4,11]]},"references-count":62,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2018,4,11]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0194098","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,4,11]]}}}