{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T02:32:38Z","timestamp":1788489158178,"version":"build-2803163510"},"reference-count":42,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2019,3,14]],"date-time":"2019-03-14T00:00:00Z","timestamp":1552521600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Head &amp; Neck"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>We sought to evaluate intratumor heterogeneity in squamous cell carcinoma of the oral cavity (OCC) and specifically determine the effect of physical separation and histologic differentiation within the same tumor.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed whole exome sequencing on five biopsy sites\u2014two from well\u2010differentiated, two from poorly differentiated regions, and one from normal parenchyma\u2014from five primary OCC specimens.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found high levels of intratumor heterogeneity and, in four primary tumors, identified only 0 to 2 <jats:italic>identical<\/jats:italic> mutations in all subsites. We found that the heterogeneity inversely correlated with physical separation and that pairs of well\u2010differentiated samples were more similar to each other than analogous poorly differentiated specimens. Only TP53 mutations, but not other purported \u201cdriver mutations\u201d in head and neck squamous cell carcinoma, were found in multiple biopsy sites.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These data highlight the challenges to characterization of the mutational landscape of OCC with single site biopsy and have implications for personalized medicine.<\/jats:p><\/jats:sec>","DOI":"10.1002\/hed.25719","type":"journal-article","created":{"date-parts":[[2019,3,14]],"date-time":"2019-03-14T15:16:36Z","timestamp":1552576596000},"page":"2514-2524","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Intratumor genetic heterogeneity in squamous cell carcinoma of the oral cavity"],"prefix":"10.1002","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1002-8301","authenticated-orcid":false,"given":"Dan P.","family":"Zandberg","sequence":"first","affiliation":[{"name":"Department of Hematology\/Oncology UPMC Hillman Cancer Center  Pittsburgh Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke J.","family":"Tallon","sequence":"additional","affiliation":[{"name":"Department of Medicine Institute for Genome Sciences, University of Maryland School of Medicine  Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sushma","family":"Nagaraj","sequence":"additional","affiliation":[{"name":"Department of Medicine Institute for Genome Sciences, University of Maryland School of Medicine  Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa K.","family":"Sadzewicz","sequence":"additional","affiliation":[{"name":"Department of Medicine Institute for Genome Sciences, University of Maryland School of Medicine  Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Public Health University of Maryland School of Medicine  Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxwell B.","family":"Strome","sequence":"additional","affiliation":[{"name":"College of Literature, Science, and the Arts University of Michigan  Ann Arbor Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuechu E.","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Medicine Institute for Genome Sciences, University of Maryland School of Medicine  Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kranthi","family":"Vavikolanu","sequence":"additional","affiliation":[{"name":"Department of Medicine Institute for Genome Sciences, University of Maryland School of Medicine  Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head and Neck Surgery University of Maryland School of Medicine  Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Papadimitriou","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Maryland School of Medicine  Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fleesie A.","family":"Hubbard","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head and Neck Surgery University of Maryland School of Medicine  Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00f8ren M.","family":"Bentzen","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Public Health University of Maryland School of Medicine  Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott E.","family":"Strome","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head and Neck Surgery University of Maryland School of Medicine  Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire M.","family":"Fraser","sequence":"additional","affiliation":[{"name":"Department of Medicine Institute for Genome Sciences, University of Maryland School of Medicine  Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,3,14]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2013.50.3870"},{"key":"e_1_2_8_3_1","first-page":"1093","article-title":"Squamous cell carcinoma of the tonsils: a molecular analysis of HPV associations","volume":"8","author":"Strome SE","year":"2002","journal-title":"Clin Cancer Res"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0912217"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1506007"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1001786"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12105-015-0617-1"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.wjorl.2016.05.007"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1406498"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa1348"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1500596"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aan6733"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf1490"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI80009"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1208130"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1206923"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14129"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2016.5054"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1113205"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09515"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1253462"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1616288"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1256930"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdu479"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp352"},{"key":"e_1_2_8_27_1","doi-asserted-by":"crossref","first-page":"11 10","DOI":"10.1002\/0471250953.bi1110s43","article-title":"From FastQ data to high confidence variant calls: the Genome Analysis Toolkit best practices pipeline","volume":"43","author":"Van der Auwera GA","year":"2013","journal-title":"Curr Protoc Bioinformatics"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2514"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.129684.111"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq603"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkr407"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku1075"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12912"},{"key":"e_1_2_8_34_1","first-page":"40","article-title":"meta: an R package for meta\u2010analysis","volume":"7","author":"Schwarzer G","year":"2007","journal-title":"R News"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.8448"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1593\/neo.131400"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.01.018"},{"key":"e_1_2_8_38_1","first-page":"2488","article-title":"Genetic progression model for head and neck cancer: implications for field cancerization","volume":"56","author":"Califano J","year":"1996","journal-title":"Cancer Res"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90186-I"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.959840"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0433-z"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09460"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2891"}],"container-title":["Head &amp; Neck"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hed.25719","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/hed.25719","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hed.25719","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,9]],"date-time":"2023-09-09T14:39:46Z","timestamp":1694270386000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/hed.25719"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,14]]},"references-count":42,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2019,8]]}},"alternative-id":["10.1002\/hed.25719"],"URL":"https:\/\/doi.org\/10.1002\/hed.25719","archive":["Portico"],"relation":{},"ISSN":["1043-3074","1097-0347"],"issn-type":[{"value":"1043-3074","type":"print"},{"value":"1097-0347","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3,14]]},"assertion":[{"value":"2018-06-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-02-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-03-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}