{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:10:27Z","timestamp":1791317427137,"version":"4.3.1"},"reference-count":72,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2021,8,6]],"date-time":"2021-08-06T00:00:00Z","timestamp":1628208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ASOPRS Foundation Grant","award":["NA"],"award-info":[{"award-number":["NA"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Ocular adnexal (OA) sebaceous carcinomas generally demonstrate more aggressive clinical and histopathological phenotypes than extraocular cases, but the molecular drivers implicated in their oncogenesis remain poorly defined. A retrospective review of surgical and ocular pathology archives identified eleven primary resection specimens of OA sebaceous carcinomas with adequate tissue for molecular analysis; two extraocular cases were also examined. Next-generation sequencing was used to evaluate mutations and copy number changes in a large panel of cancer-associated genes. Fluorescence in situ hybridization (FISH) confirmed MYC copy number gain in select cases, and immunohistochemistry to evaluate MYC protein expression. The commonest mutations occurred in TP53 (10\/13) and RB1 (7\/13). Additional mutations in clinically actionable genes, or mutations with a frequency of at least 25%, included the NF1 (3\/12), PMS2 (4\/12), ROS1 (3\/12), KMT2C (4\/12), MNX1 (6\/12), NOTCH1 (4\/12), PCLO (3\/12), and PTPRT (3\/12) loci. Low level copy number gain suggestive of amplification of the MYC locus was seen in two cases, and confirmed using FISH. MYC protein expression, as assessed by immunohistochemistry, was present in almost all sebaceous carcinoma cases. Our findings support the concept that alterations in TP53 and RB1 are the commonest alterations in sebaceous carcinoma, and suggest that MYC may contribute to the oncogenesis of these tumors.<\/jats:p>","DOI":"10.3390\/ijms22168454","type":"journal-article","created":{"date-parts":[[2021,8,6]],"date-time":"2021-08-06T08:01:42Z","timestamp":1628236902000},"page":"8454","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["NGS Analysis Confirms Common TP53 and RB1 Mutations, and Suggests MYC Amplification in Ocular Adnexal Sebaceous Carcinomas"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6550-1883","authenticated-orcid":false,"given":"Cornelia","family":"Peterson","sequence":"first","affiliation":[{"name":"Department of Molecular and Comparative Pathobiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Moore","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica L.","family":"Hicks","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura A.","family":"Morsberger","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"},{"name":"Clinical Cytogenetics Laboratory, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"},{"name":"Johns Hopkins Genomics, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo M.","family":"De Marzo","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"},{"name":"Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"},{"name":"The Brady Urological Research Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"},{"name":"Clinical Cytogenetics Laboratory, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"},{"name":"Johns Hopkins Genomics, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles G.","family":"Eberhart","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"},{"name":"Department of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley A.","family":"Campbell","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1097\/ICU.0000000000000505","article-title":"Current review of sebaceous cell carcinoma","volume":"29","author":"Orr","year":"2018","journal-title":"Curr. 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