{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T20:03:57Z","timestamp":1762459437801},"reference-count":58,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2016,11,21]],"date-time":"2016-11-21T00:00:00Z","timestamp":1479686400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Chromosomes &amp; Cancer"],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:p>Squamous cell carcinomas of the hypopharynx (HPSCC) and oropharynx (OPSCC) have markedly different patient outcomes. Differences in HPV prevalence between these two patient groups may account for some of this difference, but other molecular markers of prognosis or pathological phenotype have not been established. Copy number gain of oncogenes is a well\u2010established molecular change contributing to HNSCC development. Quantitative PCR was used to explore copy number gains of specific genes (3q\u2014<jats:italic>PIK3CA, TP63;<\/jats:italic> 11q13.3<jats:italic>\u2014CCND1, ANO1<\/jats:italic>) in tumor DNA recovered from HPSCC (<jats:italic>n =<\/jats:italic> 48) and OPSCC (<jats:italic>n =<\/jats:italic> 52) patients. Associations between copy number gain, patient demographics, HPV\/p16INK4a status and pathological stage were examined. HPV\/p16 prevalence in HPSCC and OPSCC groups was 2.1% and 46.0%, respectively. HPSCCs had frequent gains of <jats:italic>CCND1<\/jats:italic> (56.3%) and <jats:italic>ANO1<\/jats:italic> (56.3%) but few gains of <jats:italic>PIK3CA<\/jats:italic> (6.3%). By contrast, OPSCCs had significantly fewer <jats:italic>CCND1<\/jats:italic> (23.1%) and <jats:italic>ANO1<\/jats:italic> (17.3%) gains, and significantly more <jats:italic>PIK3CA<\/jats:italic> (26.9%) gains. A mutually exclusive relationship between HPV\/p16 and 11q13.3 gains was observed in OPSCCs, while <jats:italic>PIK3CA<\/jats:italic> and <jats:italic>TP63<\/jats:italic> gains were similar across HPV\u2010associated and smoking\/alcohol\u2010associated patients. <jats:italic>ANO1<\/jats:italic> gain was significantly linked to tumor pathology in HPSCC, associating with nodal metastasis and smaller and less invasive tumors at presentation (<jats:italic>P =<\/jats:italic> 0.010). Our results provide a convincing link between a specific molecular change and disease phenotype that appears unique to our HPSCC population, supporting a model of 11q13.3 in promoting metastatic disease progression in HNSCC, and suggest a role for <jats:italic>ANO1<\/jats:italic> as a molecular marker of metastatic disease. \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/gcc.22425","type":"journal-article","created":{"date-parts":[[2016,10,17]],"date-time":"2016-10-17T22:52:48Z","timestamp":1476744768000},"page":"185-198","source":"Crossref","is-referenced-by-count":9,"title":["Copy number gain of 11q13.3 genes associates with pathological stage in hypopharyngeal squamous cell carcinoma"],"prefix":"10.1002","volume":"56","author":[{"given":"Samuel B.","family":"Pattle","sequence":"first","affiliation":[{"name":"Division of Infection and Pathway Medicine The University of Edinburgh, Little France Crescent, Scotland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natasa","family":"Utjesanovic","sequence":"additional","affiliation":[{"name":"Division of Infection and Pathway Medicine The University of Edinburgh, Little France Crescent, Scotland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Athena","family":"Togo","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, The Laurieston Building NHS Lothian, Edinburgh"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucy","family":"Wells","sequence":"additional","affiliation":[{"name":"Western General Hospital The Edinburgh Cancer Centre NHS Lothian, Edinburgh"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brendan","family":"Conn","sequence":"additional","affiliation":[{"name":"Department of Pathology Royal Infirmary of Edinburgh NHS Lothian, Edinburgh"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannah","family":"Monaghan","sequence":"additional","affiliation":[{"name":"Department of Pathology Royal Infirmary of Edinburgh NHS Lothian, Edinburgh"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Junor","sequence":"additional","affiliation":[{"name":"Western General Hospital The Edinburgh Cancer Centre NHS Lothian, Edinburgh"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ingolfur","family":"Johannessen","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Royal Infirmary of Edinburgh NHS, Edinburgh"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kate","family":"Cuschieri","sequence":"additional","affiliation":[{"name":"Scottish HPV Reference Laboratory Royal Infirmary of Edinburgh NHS Lothian, Edinburgh"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon","family":"Talbot","sequence":"additional","affiliation":[{"name":"Division of Infection and Pathway Medicine The University of Edinburgh, Little France Crescent, Scotland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,11,21]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6601199"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6605823"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.3277"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.1209"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1217072110"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14129"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djv403"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/PDM.0b013e31827f3f7e"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-12-0475-T"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-010-0871-2"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djn011"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6604246"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djn025"},{"key":"e_1_2_6_15_1","first-page":"5405","article-title":"Measurement of DNA copy number at microsatellite loci using quantitative PCR analysis","volume":"60","author":"Ginzinger DG","year":"2000","journal-title":"Cancer Res"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.22214"},{"key":"e_1_2_6_17_1","unstructured":"HelliwellT WoolgarJ.2013.Royal College of Pathologists of UK Dataset for Histopathology Reporting of Mucosal Malignancies of the Pharynx. 2013. pp.13. 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