NGS Analysis Confirms Common <i>TP53</i> and <i>RB1</i> Mutations, and Suggests <i>MYC</i> Amplification in Ocular Adnexal Sebaceous Carcinomas

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...

Full description

Bibliographic Details
Main Authors: Cornelia Peterson, Robert Moore, Jessica L. Hicks, Laura A. Morsberger, Angelo M. De Marzo, Ying Zou, Charles G. Eberhart, Ashley A. Campbell
Format: Article
Language:English
Published: MDPI AG 2021-08-01
Series:International Journal of Molecular Sciences
Subjects:
sebaceous carcinoma
ocular adnexal tumor
next-generation sequencing
MYC
Online Access:https://www.mdpi.com/1422-0067/22/16/8454
Description
Summary: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.
ISSN:1661-6596
1422-0067

Similar Items