{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:38:07Z","timestamp":1790739487078,"version":"4.1.0"},"reference-count":48,"publisher":"National Academy of Sciences","issue":"47","license":[{"start":{"date-parts":[[2016,11,9]],"date-time":"2016-11-09T00:00:00Z","timestamp":1478649600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.pnas.org\/site\/misc\/userlicense.xhtml"}],"funder":[{"DOI":"10.13039\/100000054","name":"HHS | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["CA198138"],"award-info":[{"award-number":["CA198138"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"HHS | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["CA160715"],"award-info":[{"award-number":["CA160715"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2016,11,22]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    We found that gene mutations\/deletions are frequent in mesothelioma and occur through a variety of DNA alterations. We identified genes implicated in malignant mesothelioma:\n                    <jats:italic>SETD2<\/jats:italic>\n                    ,\n                    <jats:italic>SMARCC1<\/jats:italic>\n                    ,\n                    <jats:italic>PBRM1<\/jats:italic>\n                    . Previous next-generation studies (NGS) underestimated the frequency of genetic alterations in malignant mesothelioma because NGS mainly identifies nucleotide level mutations. Our findings are of general relevance to the field of cancer research that relies almost exclusively on NGS to identify gene alterations in cancer biopsies, and uses this information to design specific molecular therapies. An integrated approach that includes a high-density comparative genomic hybridization array and NGS or targeted-NGS, as conducted here, may reveal additional genes that are inactivated by mechanisms other than point mutations. This information may inform us on how to design more effective molecular therapies.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1612074113","type":"journal-article","created":{"date-parts":[[2016,11,10]],"date-time":"2016-11-10T09:10:31Z","timestamp":1478769031000},"page":"13432-13437","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":133,"title":["High-density array-CGH with targeted NGS unmask multiple noncontiguous minute deletions on chromosome 3p21 in mesothelioma"],"prefix":"10.1073","volume":"113","author":[{"given":"Yoshie","family":"Yoshikawa","sequence":"first","affiliation":[{"name":"Department of Genetics, Hyogo College of Medicine, Nishinomiya, Hyogo J663-8501, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuru","family":"Emi","sequence":"additional","affiliation":[{"name":"Department of Genetics, Hyogo College of Medicine, Nishinomiya, Hyogo J663-8501, Japan;"},{"name":"Thoracic Oncology Program, University of Hawaii Cancer Center, Honolulu, HI 96813;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Hashimoto-Tamaoki","sequence":"additional","affiliation":[{"name":"Department of Genetics, Hyogo College of Medicine, Nishinomiya, Hyogo J663-8501, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaki","family":"Ohmuraya","sequence":"additional","affiliation":[{"name":"Department of Genetics, Hyogo College of Medicine, Nishinomiya, Hyogo J663-8501, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayuko","family":"Sato","sequence":"additional","affiliation":[{"name":"Division of Molecular Pathology, Department of Pathology, Hyogo College of Medicine, Nishinomiya, Hyogo J663-8501, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tohru","family":"Tsujimura","sequence":"additional","affiliation":[{"name":"Division of Molecular Pathology, Department of Pathology, Hyogo College of Medicine, Nishinomiya, Hyogo J663-8501, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seiki","family":"Hasegawa","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo J663-8501, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Nakano","sequence":"additional","affiliation":[{"name":"Division of Respiratory Medicine, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo J663-8501, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaki","family":"Nasu","sequence":"additional","affiliation":[{"name":"Thoracic Oncology Program, University of Hawaii Cancer Center, Honolulu, HI 96813;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Pastorino","sequence":"additional","affiliation":[{"name":"Thoracic Oncology Program, University of Hawaii Cancer Center, Honolulu, HI 96813;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agata","family":"Szymiczek","sequence":"additional","affiliation":[{"name":"Thoracic Oncology Program, University of Hawaii Cancer Center, Honolulu, HI 96813;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Bononi","sequence":"additional","affiliation":[{"name":"Thoracic Oncology Program, University of Hawaii Cancer Center, Honolulu, HI 96813;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mika","family":"Tanji","sequence":"additional","affiliation":[{"name":"Thoracic Oncology Program, University of Hawaii Cancer Center, Honolulu, HI 96813;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Pagano","sequence":"additional","affiliation":[{"name":"Thoracic Oncology Program, University of Hawaii Cancer Center, Honolulu, HI 96813;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Gaudino","sequence":"additional","affiliation":[{"name":"Thoracic Oncology Program, University of Hawaii Cancer Center, Honolulu, HI 96813;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Napolitano","sequence":"additional","affiliation":[{"name":"Thoracic Oncology Program, University of Hawaii Cancer Center, Honolulu, HI 96813;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandra","family":"Goparaju","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, New York University Langone Medical Center, New York, NY 10016"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harvey I.","family":"Pass","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, New York University Langone Medical Center, New York, NY 10016"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haining","family":"Yang","sequence":"additional","affiliation":[{"name":"Thoracic Oncology Program, University of Hawaii Cancer Center, Honolulu, HI 96813;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Carbone","sequence":"additional","affiliation":[{"name":"Thoracic Oncology Program, University of Hawaii Cancer Center, Honolulu, HI 96813;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2016,11,9]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2016.04.028"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1005633"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.3816\/CLC.2003.n.031"},{"key":"e_1_3_3_4_2","first-page":"875","article-title":"Simian virus 40: The link with human malignant mesothelioma is well established","volume":"20","author":"Carbone M","year":"2000","unstructured":"M Carbone, P Rizzo, H Pass, Simian virus 40: The link with human malignant mesothelioma is well established. Anticancer Res 20, 875\u2013877 (2000).","journal-title":"Anticancer Res"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0046091"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-1130"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2016.07.004"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers7030837"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-14-1008"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1097\/JTO.0000000000000436"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3520"},{"key":"e_1_3_3_12_2","first-page":"2331","article-title":"Genome-based mutational analysis by next generation sequencing in patients with malignant pleural and peritoneal mesothelioma","volume":"36","author":"Ugurluer G","year":"2016","unstructured":"G Ugurluer, , Genome-based mutational analysis by next generation sequencing in patients with malignant pleural and peritoneal mesothelioma. Anticancer Res 36, 2331\u20132338 (2016).","journal-title":"Anticancer Res"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.855"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.912"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1097\/JTO.0b013e31829e7ef9"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1097\/JTO.0000000000000466"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.03.002"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.2011-0215-RA"},{"key":"e_1_3_3_19_2","first-page":"4349","article-title":"Recurrent deletions of specific chromosomal sites in 1p, 3p, 6q, and 9p in human malignant mesothelioma","volume":"53","author":"Taguchi T","year":"1993","unstructured":"T Taguchi, SC Jhanwar, JM Siegfried, SM Keller, JR Testa, Recurrent deletions of specific chromosomal sites in 1p, 3p, 6q, and 9p in human malignant mesothelioma. Cancer Res 53, 4349\u20134355 (1993).","journal-title":"Cancer Res"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2012.02223.x"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1097\/JTO.0000000000000471"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.2870110104"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1159\/000109618"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2006.00386.x"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.23949"},{"key":"e_1_3_3_26_2","first-page":"1365","article-title":"Frequent deletion of 3p21.1 region carrying semaphorin 3G and aberrant expression of the genes participating in semaphorin signaling in the epithelioid type of malignant mesothelioma cells","volume":"39","author":"Yoshikawa Y","year":"2011","unstructured":"Y Yoshikawa, , Frequent deletion of 3p21.1 region carrying semaphorin 3G and aberrant expression of the genes participating in semaphorin signaling in the epithelioid type of malignant mesothelioma cells. Int J Oncol 39, 1365\u20131374 (2011).","journal-title":"Int J Oncol"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1210547"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/470476a"},{"key":"e_1_3_3_29_2","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1002\/ijc.29015","article-title":"Biallelic germline and somatic mutations in malignant mesothelioma: Multiple mutations in transcription regulators including mSWI\/SNF genes","volume":"136","author":"Yoshikawa Y","year":"2015","unstructured":"Y Yoshikawa, , Biallelic germline and somatic mutations in malignant mesothelioma: Multiple mutations in transcription regulators including mSWI\/SNF genes. Int J Cancer 136, 560\u2013571 (2015).","journal-title":"Int J Cancer"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature08672"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09639"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.6171"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3409"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13148-015-0091-3"},{"key":"e_1_3_3_35_2","article-title":"SETD2: An epigenetic modifier with tumor suppressor functionality","author":"Li J","year":"2016","unstructured":"J Li, , SETD2: An epigenetic modifier with tumor suppressor functionality. Oncotarget, May 14, 2016).","journal-title":"Oncotarget"},{"key":"e_1_3_3_36_2","doi-asserted-by":"crossref","unstructured":"H Parker Genomic disruption of the histone methyltransferase SETD2 in chronic lymphocytic leukaemia. Leukemia . (June 10 2016).","DOI":"10.1038\/leu.2016.134"},{"key":"e_1_3_3_37_2","article-title":"SETD2 histone modifier loss in aggressive GI stromal tumours","author":"Huang KK","year":"2015","unstructured":"KK Huang, , SETD2 histone modifier loss in aggressive GI stromal tumours. Gut, September 3, 2015).","journal-title":"Gut"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2813"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2013.12.017"},{"key":"e_1_3_3_40_2","first-page":"9307","article-title":"Low PBRM1 identifies tumor progression and poor prognosis in breast cancer","volume":"8","author":"Mo D","year":"2015","unstructured":"D Mo, , Low PBRM1 identifies tumor progression and poor prognosis in breast cancer. Int J Clin Exp Pathol 8, 9307\u20139313 (2015).","journal-title":"Int J Clin Exp Pathol"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.4161\/epi.6.12.18492"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2015.243"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1414789111"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature19057"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.22724"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3459"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.02.012"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.arcmed.2014.10.005"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.1612074113","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1612074113","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,20]],"date-time":"2024-06-20T10:00:06Z","timestamp":1718877606000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1612074113"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,11,9]]},"references-count":48,"journal-issue":{"issue":"47","published-print":{"date-parts":[[2016,11,22]]}},"alternative-id":["10.1073\/pnas.1612074113"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1612074113","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,11,9]]},"assertion":[{"value":"2016-11-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}