NGS Analysis Confirms Common and Mutations, and Suggests 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 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 copy number gain in select cases, and immunohistochemistry to evaluate MYC protein expression. The commonest mutations occurred in (10/13) and (7/13). Additional mutations in clinically actionable genes, or mutations with a frequency of at least 25%, included the (3/12), (4/12), (3/12), (4/12), (6/12), (4/12), (3/12), and (3/12) loci. Low level copy number gain suggestive of amplification of the 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 and are the commonest alterations in sebaceous carcinoma, and suggest that may contribute to the oncogenesis of these tumors.