{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T20:56:44Z","timestamp":1789419404876,"version":"build-2803163510"},"reference-count":33,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,7,8]],"date-time":"2021-07-08T00:00:00Z","timestamp":1625702400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100005292","name":"Brigham and Women's Hospital","doi-asserted-by":"publisher","award":["#2018P001007"],"award-info":[{"award-number":["#2018P001007"]}],"id":[{"id":"10.13039\/100005292","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Oesophageal verrucous carcinoma (VSCC) is a rare and morphologically distinct type of oesophageal squamous cell carcinoma (SCC). Diagnosing VSCC on biopsy material is challenging, given the lack of significant atypia and the presence of keratinising epithelium and exophytic growth. The molecular pathogenesis of VSCC remains unclear. The aim of this study was to characterise the genomic landscape of VSCC in comparison to conventional oesophageal SCC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>Three cases of VSCC from the Brigham and Women\u2019s Hospital pathology archive were identified. Formalin\u2010fixed, paraffin\u2010embedded (FFPE) tumour tissue was used for p16 immunohistochemistry (IHC), high\u2010risk human papillomavirus (HPV) <jats:italic>in\u2010situ<\/jats:italic> mRNA hybridisation (ISH) and DNA isolation. Tumour DNA was sequenced using a targeted massively parallel sequencing assay enriched for cancer\u2010associated genes. Three additional cases of VSCC were identified by image review of The Cancer Genome Atlas (TCGA) oesophageal SCC cohort. VSCC cases were negative for p16 IHC and high\u2010risk HPV ISH. TP53 mutations (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001) and copy number variants (CNVs) for <jats:italic>CDKN2A<\/jats:italic> (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001), <jats:italic>CDKN2B<\/jats:italic> (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01) and <jats:italic>CCND1<\/jats:italic> (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01) were absent in VSCC and significantly less frequent in comparison to conventional SCC. Five VSCC cases featured <jats:italic>SMARCA4<\/jats:italic> missense mutations or in\u2010frame deletions compared to only four of 88 conventional SCC cases (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001). VSCC featured driver mutations in <jats:italic>PIK3CA<\/jats:italic>, <jats:italic>HRAS<\/jats:italic> and <jats:italic>GNAS<\/jats:italic>. Recurrent CNVs were rare in VSCC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>VSCC is not only morphologically but also genetically distinct from conventional oesophageal SCC, featuring frequent <jats:italic>SMARCA4<\/jats:italic> mutations and infrequent <jats:italic>TP53<\/jats:italic> mutations or <jats:italic>CDKN2A\/B<\/jats:italic> CNVs. Molecular findings may aid in establishing the challenging diagnosis of VSCC.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.14395","type":"journal-article","created":{"date-parts":[[2021,5,8]],"date-time":"2021-05-08T19:08:04Z","timestamp":1620500884000},"page":"642-649","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Verrucous carcinoma of the oesophagus is a genetically distinct subtype of oesophageal squamous cell carcinoma"],"prefix":"10.1111","volume":"79","author":[{"given":"Raymond A","family":"Isidro","sequence":"first","affiliation":[{"name":"Department of Pathology Brigham and Women\u2019s Hospital Boston MA USA"},{"name":"Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Pathology Brigham and Women\u2019s Hospital Boston MA USA"},{"name":"Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason L","family":"Hornick","sequence":"additional","affiliation":[{"name":"Department of Pathology Brigham and Women\u2019s Hospital Boston MA USA"},{"name":"Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon O","family":"Wee","sequence":"additional","affiliation":[{"name":"Harvard Medical School Boston MA USA"},{"name":"Department of Surgery Brigham and Women\u2019s Hospital Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agoston","family":"Agoston","sequence":"additional","affiliation":[{"name":"Department of Pathology Brigham and Women\u2019s Hospital Boston MA USA"},{"name":"Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepa T.","family":"Patil","sequence":"additional","affiliation":[{"name":"Department of Pathology Brigham and Women\u2019s Hospital Boston MA USA"},{"name":"Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vikram","family":"Deshpande","sequence":"additional","affiliation":[{"name":"Harvard Medical School Boston MA USA"},{"name":"Department of Pathology Massachusetts General Hospital Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4322-6475","authenticated-orcid":false,"given":"Lei","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pathology Brigham and Women\u2019s Hospital Boston MA USA"},{"name":"Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,7,8]]},"reference":[{"key":"e_1_2_7_2_1","volume-title":"SEER Cancer Statistics Review, 1975\u20132017","author":"Howlader 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