NGS Analysis Confirms Common TP53 and RB1 Mutations, and Suggests MYC Amplification in Ocular Adnexal Sebaceous Carcinomas.

Abstract

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.

• Authors: Cornelia Peterson, Robert Moore, Jessica L Hicks, Laura A Morsberger, Angelo M De Marzo, Ying Zou, Charles G Eberhart, Ashley A Campbell
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 22 Issue 16 (Aug 06 2021) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 34445161 (Publication Type: Journal Article)

Chemical References

• MYC protein, human
• Proto-Oncogene Proteins c-myc
• RB1 protein, human
• Retinoblastoma Binding Proteins
• TP53 protein, human
• Tumor Suppressor Protein p53
• Ubiquitin-Protein Ligases

Topics

• Aged
• Aged, 80 and over
• Eye Neoplasms (genetics)
• Female
• Gene Dosage
• High-Throughput Nucleotide Sequencing
• Humans
• Male
• Middle Aged
• Mutation
• Neoplasms, Adnexal and Skin Appendage (genetics)
• Proto-Oncogene Proteins c-myc (genetics)
• Retinoblastoma Binding Proteins (genetics)
• Sebaceous Gland Neoplasms (genetics)
• Tumor Suppressor Protein p53 (genetics)
• Ubiquitin-Protein Ligases (genetics)