TERT promoter mutation in sebaceous neoplasms

Virchows Arch. 2021 Sep;479(3):551-558. doi: 10.1007/s00428-021-03083-9. Epub 2021 Mar 25.

Abstract

TERT promoter (TERTp) mutations widely occur in multiple human neoplasms, and they have been related to different clinicopathological features. To date, this mutation has not been identified in sebaceous tumors. Here, we analyzed TERTp mutations in 91 sebaceous neoplasms (17 adenomas, 45 sebaceomas, and 29 carcinomas). We detected mutations in 26.7% (8 of 29) of sebaceous carcinomas by pyrosequencing and Sanger sequencing. No mutation was detected in adenomas or sebaceomas. The difference was significant between sebaceoma and carcinoma. The most frequent TERTp mutations were C228T and C250T in 37.5% (3 of 8) of mutated cases each one. The mutation was not associated with poor clinical evolution. Using NGS, 20 of 29 (68.5%) sebaceous carcinomas harbored mutations in 8 of the 30 genes analyzed (TP53, TERTp, EGFR, ATRX, PDGFRA, CDKN2A, PTEN, and ACVR1). With immunohistochemistry, only 1 of 8 (12.5%) TERTp-mutated carcinomas lacked mismatch repair (MMR) protein expression compared to 6 of 21 (31.6%) of non-mutated ones. Sebaceous carcinomas with MMR protein expression had significantly higher frequency of total mutations and TP53 and TERTp mutations than MMR protein-deficient carcinomas. In conclusion, TERTp mutation has been detected in sebaceous carcinomas, and its presence could be useful to differentiate sebaceous carcinoma from sebaceoma, a difficult histopathological challenge.

Keywords: Mismatch repair proteins; Sebaceous neoplasms; Sequencing; TERT promoter mutation.

MeSH terms

  • Adenoma / chemistry
  • Adenoma / genetics*
  • Adenoma / pathology
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics*
  • Carcinoma / chemistry
  • Carcinoma / genetics*
  • Carcinoma / pathology
  • DNA Mismatch Repair
  • DNA Mutational Analysis
  • Female
  • Genetic Predisposition to Disease
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Mutation*
  • Phenotype
  • Promoter Regions, Genetic*
  • Sebaceous Gland Neoplasms / chemistry
  • Sebaceous Gland Neoplasms / genetics*
  • Sebaceous Gland Neoplasms / pathology
  • Telomerase / genetics*
  • Tumor Suppressor Protein p53 / genetics

Substances

  • Biomarkers, Tumor
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • TERT protein, human
  • Telomerase