{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T15:06:11Z","timestamp":1792681571317,"version":"4.5.0"},"reference-count":36,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T00:00:00Z","timestamp":1671753600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012503","name":"Royal Hobart Hospital Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012503","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes Chromosomes &amp; Cancer"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Recurrent tumor copy number variations (CNVs) in prostate cancer (PrCa) have predominantly been discovered in sporadic tumor cohorts. Here, we examined familial prostate tumors for novel CNVs as prior studies suggest these harbor distinct CNVs. Array comparative genomic hybridization of 12 tumors from an Australian PrCa family, PcTas9, highlighted multiple recurrent CNVs, including amplification of <jats:italic>EEF2<\/jats:italic> (19p13.3) in 100% of tumors. The <jats:italic>EEF2<\/jats:italic> CNV was examined in a further 26 familial and seven sporadic tumors from the Australian cohort and in 494 tumors unselected for family history from The Cancer Genome Atlas (TCGA). <jats:italic>EEF2<\/jats:italic> overexpression was observed in seven PcTas9 tumors, in addition to seven other predominantly familial tumors (<jats:italic>n<\/jats:italic><jats:sub>total<\/jats:sub>\u00a0=\u200934%). <jats:italic>EEF2<\/jats:italic> amplification was only observed in 1.4% of TCGA tumors, however 7.5% harbored an <jats:italic>EEF2<\/jats:italic> deletion. Analysis of genes co\u2010expressed with <jats:italic>EEF2<\/jats:italic> revealed significant upregulation of two genes, <jats:italic>ZNF74<\/jats:italic> and <jats:italic>ADSL,<\/jats:italic> and downregulation of <jats:italic>PLSCR1<\/jats:italic> in both <jats:italic>EEF2<\/jats:italic> amplified familial tumors and <jats:italic>EEF2<\/jats:italic> deleted TCGA tumors. Furthermore, in TCGA tumors, <jats:italic>EEF2<\/jats:italic> amplification and deletion were significantly associated with a higher Gleason score. In summary, we identified a novel PrCa CNV that was predominantly amplified in familial tumors and deleted in unselected tumors. Our results provide further evidence that familial tumors harbor distinct CNVs, potentially due to an inherited predisposition, but also suggest that regardless of how <jats:italic>EEF2<\/jats:italic> is dysregulated, a similar set of genes involved in key cancer pathways are impacted. Given the current lack of gene\u2010based biomarkers and clinical targets in PrCa, further investigation of <jats:italic>EEF2<\/jats:italic> is warranted.<\/jats:p>","DOI":"10.1002\/gcc.23117","type":"journal-article","created":{"date-parts":[[2022,12,15]],"date-time":"2022-12-15T15:43:37Z","timestamp":1671119017000},"page":"247-255","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Identification of a novel recurrent <scp><i>EEF2<\/i><\/scp> gene amplification in familial prostate tumors"],"prefix":"10.1002","volume":"62","author":[{"given":"Kelsie","family":"Raspin","sequence":"first","affiliation":[{"name":"Menzies Institute for Medical Research University of Tasmania  Hobart Tasmania Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James R.","family":"Marthick","sequence":"additional","affiliation":[{"name":"Menzies Institute for Medical Research University of Tasmania  Hobart Tasmania Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaun","family":"Donovan","sequence":"additional","affiliation":[{"name":"Diagnostic Services Sonic Healthcare  Hobart Tasmania Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leigh","family":"Blizzard","sequence":"additional","affiliation":[{"name":"Menzies Institute for Medical Research University of Tasmania  Hobart Tasmania Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roslyn C.","family":"Malley","sequence":"additional","affiliation":[{"name":"Diagnostic Services Sonic Healthcare  Hobart Tasmania Australia"},{"name":"Tasmanian School of Medicine University of Tasmania  Hobart Tasmania Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chol\u2010hee","family":"Jung","sequence":"additional","affiliation":[{"name":"Melbourne Bioinformatics University of Melbourne  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Banks","sequence":"additional","affiliation":[{"name":"Menzies Institute for Medical Research University of Tasmania  Hobart Tasmania Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Redwig","sequence":"additional","affiliation":[{"name":"Department of Urology Royal Hobart Hospital  Hobart Tasmania Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marketa","family":"Skala","sequence":"additional","affiliation":[{"name":"WP Holman Clinic Royal Hobart Hospital  Hobart Tasmania Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne L.","family":"Dickinson","sequence":"additional","affiliation":[{"name":"Menzies Institute for Medical Research University of Tasmania  Hobart Tasmania Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6882-2698","authenticated-orcid":false,"given":"Liesel M.","family":"FitzGerald","sequence":"additional","affiliation":[{"name":"Menzies Institute for Medical Research University of Tasmania  Hobart Tasmania Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,12,23]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1586\/14737159.2015.1013032"},{"key":"e_1_2_10_3_1","first-page":"96","article-title":"Molecular cytogenetics: an indispensable tool for cancer diagnosis","volume":"35","author":"Wan TS","year":"2012","journal-title":"Chang Gung Med J"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.20543"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cancergen.2014.09.003"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-4608(00)00276-4"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0045(20010215)46:3<233::AID-PROS1028>3.0.CO;2-W"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-18217-w"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2021.09.038"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.33584"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.24300"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.5114\/wo.2014.47136"},{"issue":"291","key":"e_1_2_10_13_1","article-title":"Cell\u2010of\u2010origin patterns dominate the molecular classification of 10,000 tumors from 33 types of cancer","volume":"173","author":"Hoadley KA","year":"2018","journal-title":"Cell"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41374-017-0001-8"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/030089160909500315"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63118-5"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.20263"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1086\/321281"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.10303"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1189"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12253-017-0302-7"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.12.078"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-09-0772"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2022.06.010"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03573-6"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0197-87"},{"key":"e_1_2_10_27_1","first-page":"41","article-title":"Comparative genomic hybridization: a rapid new method for detecting and mapping DNA amplification in tumors","volume":"4","author":"Kallioniemi OP","year":"1993","journal-title":"Semin Cancer Biol"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.pcan.4500401"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tice.2018.05.014"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.72.110601.135450"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1499-3872(12)60197-0"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-022-00895-3"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-10-254"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2020.12225"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2016.09.009"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1159\/000356604"},{"key":"e_1_2_10_37_1","first-page":"9943571","article-title":"Identification of key genes and pathways involved in circulating tumor cells in colorectal cancer","volume":"2022","author":"Pan R","year":"2022","journal-title":"Anal Cell Pathol (Amst)"}],"container-title":["Genes, Chromosomes and Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/gcc.23117","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/gcc.23117","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/gcc.23117","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,17]],"date-time":"2023-08-17T18:33:04Z","timestamp":1692297184000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/gcc.23117"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,23]]},"references-count":36,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2023,5]]}},"alternative-id":["10.1002\/gcc.23117"],"URL":"https:\/\/doi.org\/10.1002\/gcc.23117","archive":["Portico"],"relation":{},"ISSN":["1045-2257","1098-2264"],"issn-type":[{"value":"1045-2257","type":"print"},{"value":"1098-2264","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,23]]},"assertion":[{"value":"2022-10-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-12-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-12-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}