NGS Analysis Confirms Common <i>TP53</i> and <i>RB1</i> Mutations, and Suggests <i>MYC</i> Amplification in Ocular Adnexal Sebaceous Carcinomas
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 identifie...
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MDPI AG
2021-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/16/8454 |
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| author | Cornelia Peterson Robert Moore Jessica L. Hicks Laura A. Morsberger Angelo M. De Marzo Ying Zou Charles G. Eberhart Ashley A. Campbell |
| author_facet | Cornelia Peterson Robert Moore Jessica L. Hicks Laura A. Morsberger Angelo M. De Marzo Ying Zou Charles G. Eberhart Ashley A. Campbell |
| author_sort | Cornelia Peterson |
| collection | DOAJ |
| description | 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 <i>MYC</i> copy number gain in select cases, and immunohistochemistry to evaluate MYC protein expression. The commonest mutations occurred in <i>TP53</i> (10/13) and <i>RB1</i> (7/13). Additional mutations in clinically actionable genes, or mutations with a frequency of at least 25%, included the <i>NF1</i> (3/12), <i>PMS2</i> (4/12), <i>ROS1</i> (3/12), <i>KMT2C</i> (4/12), <i>MNX1</i> (6/12), <i>NOTCH1</i> (4/12), <i>PCLO</i> (3/12), and <i>PTPRT</i> (3/12) loci. Low level copy number gain suggestive of amplification of the <i>MYC</i> 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 <i>TP53</i> and <i>RB1</i> are the commonest alterations in sebaceous carcinoma, and suggest that <i>MYC</i> may contribute to the oncogenesis of these tumors. |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-c0f0d587b7794b68b19c6d4dea9f114c2023-11-22T07:55:22ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-08-012216845410.3390/ijms22168454NGS Analysis Confirms Common <i>TP53</i> and <i>RB1</i> Mutations, and Suggests <i>MYC</i> Amplification in Ocular Adnexal Sebaceous CarcinomasCornelia Peterson0Robert Moore1Jessica L. Hicks2Laura A. Morsberger3Angelo M. De Marzo4Ying Zou5Charles G. Eberhart6Ashley A. Campbell7Department of Molecular and Comparative Pathobiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USADepartment of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USADepartment of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USADepartment of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USADepartment of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USADepartment of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USADepartment of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USADepartment of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USAOcular 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 <i>MYC</i> copy number gain in select cases, and immunohistochemistry to evaluate MYC protein expression. The commonest mutations occurred in <i>TP53</i> (10/13) and <i>RB1</i> (7/13). Additional mutations in clinically actionable genes, or mutations with a frequency of at least 25%, included the <i>NF1</i> (3/12), <i>PMS2</i> (4/12), <i>ROS1</i> (3/12), <i>KMT2C</i> (4/12), <i>MNX1</i> (6/12), <i>NOTCH1</i> (4/12), <i>PCLO</i> (3/12), and <i>PTPRT</i> (3/12) loci. Low level copy number gain suggestive of amplification of the <i>MYC</i> 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 <i>TP53</i> and <i>RB1</i> are the commonest alterations in sebaceous carcinoma, and suggest that <i>MYC</i> may contribute to the oncogenesis of these tumors.https://www.mdpi.com/1422-0067/22/16/8454sebaceous carcinomaocular adnexal tumornext-generation sequencingMYC |
| spellingShingle | Cornelia Peterson Robert Moore Jessica L. Hicks Laura A. Morsberger Angelo M. De Marzo Ying Zou Charles G. Eberhart Ashley A. Campbell NGS Analysis Confirms Common <i>TP53</i> and <i>RB1</i> Mutations, and Suggests <i>MYC</i> Amplification in Ocular Adnexal Sebaceous Carcinomas International Journal of Molecular Sciences sebaceous carcinoma ocular adnexal tumor next-generation sequencing MYC |
| title | NGS Analysis Confirms Common <i>TP53</i> and <i>RB1</i> Mutations, and Suggests <i>MYC</i> Amplification in Ocular Adnexal Sebaceous Carcinomas |
| title_full | NGS Analysis Confirms Common <i>TP53</i> and <i>RB1</i> Mutations, and Suggests <i>MYC</i> Amplification in Ocular Adnexal Sebaceous Carcinomas |
| title_fullStr | NGS Analysis Confirms Common <i>TP53</i> and <i>RB1</i> Mutations, and Suggests <i>MYC</i> Amplification in Ocular Adnexal Sebaceous Carcinomas |
| title_full_unstemmed | NGS Analysis Confirms Common <i>TP53</i> and <i>RB1</i> Mutations, and Suggests <i>MYC</i> Amplification in Ocular Adnexal Sebaceous Carcinomas |
| title_short | NGS Analysis Confirms Common <i>TP53</i> and <i>RB1</i> Mutations, and Suggests <i>MYC</i> Amplification in Ocular Adnexal Sebaceous Carcinomas |
| title_sort | ngs analysis confirms common i tp53 i and i rb1 i mutations and suggests i myc i amplification in ocular adnexal sebaceous carcinomas |
| topic | sebaceous carcinoma ocular adnexal tumor next-generation sequencing MYC |
| url | https://www.mdpi.com/1422-0067/22/16/8454 |
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