TERT promoter mutation in sebaceous neoplasms

Area of Science:

• Oncology
• Dermatopathology
• Cancer Genomics

Background:

• TERT promoter (TERTp) mutations are common in many cancers but previously unobserved in sebaceous neoplasms.
• Sebaceous tumors, including adenomas, sebaceomas, and carcinomas, present diagnostic challenges.
• Understanding genetic alterations in sebaceous neoplasms is crucial for accurate diagnosis and treatment.

Purpose of the Study:

• To investigate the presence and significance of TERT promoter mutations in various sebaceous tumors.
• To determine if TERT promoter mutations can differentiate between benign and malignant sebaceous neoplasms.
• To explore the mutational landscape and its correlation with mismatch repair (MMR) status in sebaceous carcinomas.

Main Methods:

• Analysis of TERT promoter mutations in 91 sebaceous neoplasms (adenomas, sebaceomas, carcinomas) using pyrosequencing and Sanger sequencing.
• Next-generation sequencing (NGS) was employed to analyze mutations in 30 genes in sebaceous carcinomas.
• Immunohistochemistry was used to assess mismatch repair (MMR) protein expression in relation to TERT promoter mutations.

Main Results:

• TERT promoter mutations were detected in 26.7% of sebaceous carcinomas but not in adenomas or sebaceomas.
• The most common TERT promoter mutations were C228T and C250T.
• NGS revealed mutations in 8 of 30 genes in 68.5% of sebaceous carcinomas, with TP53 and TERTp being frequent.
• TERT promoter-mutated carcinomas showed a trend towards intact MMR protein expression.

Conclusions:

• TERT promoter mutations are a distinct feature of sebaceous carcinomas, absent in benign counterparts.
• TERT promoter mutation status can serve as a valuable biomarker to differentiate sebaceous carcinoma from sebaceoma.
• The genetic profile, including TERT promoter and TP53 mutations, may influence MMR deficiency in sebaceous carcinomas.