{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T17:22:35Z","timestamp":1789665755586,"version":"4.0.1"},"reference-count":45,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,3,30]],"date-time":"2016-03-30T00:00:00Z","timestamp":1459296000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"National Institute of Dental and Craniofacial Research and National Institute of Health","award":["R01 DE023347 (to J.A.C.)"],"award-info":[{"award-number":["R01 DE023347 (to J.A.C.)"]}]},{"name":"National Institute of Dental and Craniofacial Research and National Cancer Institute","award":["P50 DE 019032 (to J.A.C.)"],"award-info":[{"award-number":["P50 DE 019032 (to J.A.C.)"]}]},{"name":"National Institute of Dental Craniofacial Research Training","award":["2T32DC000027-26 (to T.G.)"],"award-info":[{"award-number":["2T32DC000027-26 (to T.G.)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2016,7,15]]},"abstract":"<jats:p>The Cancer Genome Atlas (TCGA) sequencing analysis of head and neck squamous cell carcinoma (HNSCC) recently reported on gene fusions, however, few human papillomavirus (HPV) positive samples were included, and the functional relevance of identified fusions was not explored. We therefore performed an independent analysis of gene fusions in HPV\u2010positive oropharyngeal SCC (OPSCC). RNA sequencing was performed on 47 HPV\u2010positive OPSCC primary tumors and 25 normal mucosal samples from cancer unaffected controls on an Illumina TruSeq platform. MapSplice2 was used for alignment and identification of fusion candidates. Putative fusions with less than five spanning reads, detected in normal tissues, or that mapped to the same gene were filtered out. Selected fusions were validated by RT\u2010PCR and Sanger sequencing. Within 47 HPV\u2010positive OPSCC tumors, 282 gene fusions were identified. Most fusions (85.1%) occurred in a single tumor, and the remaining fusions recurred in 2\u201316 tumors. Gene fusions were associated with significant up regulation of 16 genes (including <jats:italic>EGFR<\/jats:italic> and <jats:italic>ERBB4<\/jats:italic>) and down regulation of four genes (<jats:italic>PTPRT, ZNF750, DLG2, SLCO5A1<\/jats:italic>). Expression of these genes followed similar patterns of up regulation and down regulation in tumors without these fusions compared to normal tissue. Five of six gene fusions selected for validation were confirmed through RT\u2010PCR and sequencing. This integrative analysis provides a method of prioritizing functionally relevant gene fusions that may be expanded to other tumor types. These results demonstrate that gene fusions may be one mechanism by which functionally relevant genes are altered in HPV\u2010positive OPSCC.<\/jats:p>","DOI":"10.1002\/ijc.30081","type":"journal-article","created":{"date-parts":[[2016,3,7]],"date-time":"2016-03-07T23:00:59Z","timestamp":1457391659000},"page":"373-382","source":"Crossref","is-referenced-by-count":53,"title":["Characterization of functionally active gene fusions in human papillomavirus related oropharyngeal squamous cell carcinoma"],"prefix":"10.1002","volume":"139","author":[{"given":"Theresa","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Otolaryngology\u2014Head and Neck Surgery Johns Hopkins Medical Institutions Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daria A.","family":"Gaykalova","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2014Head and Neck Surgery Johns Hopkins Medical Institutions Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Considine","sequence":"additional","affiliation":[{"name":"Division of Oncology Biostatistics, Department of Oncology Johns Hopkins Medical Institutions Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Wheelan","sequence":"additional","affiliation":[{"name":"Division of Oncology Biostatistics, Department of Oncology Johns Hopkins Medical Institutions Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aparna","family":"Pallavajjala","sequence":"additional","affiliation":[{"name":"Division of Oncology Biostatistics, Department of Oncology Johns Hopkins Medical Institutions Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin A","family":"Bishop","sequence":"additional","affiliation":[{"name":"Department of Pathology Johns Hopkins Medical Institutions Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William H.","family":"Westra","sequence":"additional","affiliation":[{"name":"Department of Pathology Johns Hopkins Medical Institutions Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trey","family":"Ideker","sequence":"additional","affiliation":[{"name":"Department of Medicine University of California San Diego San Diego CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wayne M","family":"Koch","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2014Head and Neck Surgery Johns Hopkins Medical Institutions Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zubair","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2014Head and Neck Surgery Johns Hopkins Medical Institutions Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elana J.","family":"Fertig","sequence":"additional","affiliation":[{"name":"Division of Oncology Biostatistics, Department of Oncology Johns Hopkins Medical Institutions Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph A.","family":"Califano","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2014Head and Neck Surgery Johns Hopkins Medical Institutions Baltimore MD"},{"name":"Division of Otolaryngology\u2014Head and Neck Surgery, Department of Surgery Moores Cancer Center, University of California San Diego CA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,3,30]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21254"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2008.06.002"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.20141"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.14.1713"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0912217"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdu167"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.28847"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1206923"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1208130"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14129"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07638"},{"key":"e_1_2_6_13_1","first-page":"7003","article-title":"Novel chromosomal rearrangements and break points at the t(6;9) in salivary adenoid cystic carcinoma: association with MYB\u2010NFIB chimeric fusion, MYB expression, and clinical outcome. 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