TERT promoter mutations are frequent in atypical fibroxanthomas and pleomorphic dermal sarcomas

Mod Pathol. 2014 Apr;27(4):502-8. doi: 10.1038/modpathol.2013.168. Epub 2013 Sep 13.


Activating mutations in the TERT promoter leading to increased telomerase expression were recently identified in cutaneous melanoma and subsequently in many other types of cancer. These mutations lead to increased telomerase expression, allowing cells to proliferate continuously without entering apoptosis or senescence. Atypical fibroxanthomas and pleomorphic dermal sarcomas are genetically poorly understood tumors developing in the skin of older patients. Known genetic events in these tumors are mutations in TP53 (atypical fibroxanthoma and pleomorphic dermal sarcoma) and RAS (pleomorphic dermal sarcoma) genes, often having a UV signature. We analyzed a cohort of 27 atypical fibroxanthomas and 34 pleomorphic dermal sarcomas for the presence of TERT promoter mutations by conventional Sanger sequencing. TERT promoter mutations were identified in 25 (93%) atypical fibroxanthomas and in 26 (76%) pleomorphic dermal sarcomas. Mutations were found to have a UV signature (C>T or CC>TT) and were largely identical to those detected in cutaneous melanoma. Our data show that TERT promoter mutations are the most frequent mutations in atypical fibroxanthomas and pleomorphic dermal sarcomas reported to date. The identified mutations confirm the pathogenetic role of UV exposure in both atypical fibroxanthomas and pleomorphic dermal sarcomas and suggest that telomere maintenance through increased expression of telomerase plays an important role in the pathogenesis of these tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • DNA Mutational Analysis
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Promoter Regions, Genetic*
  • Sarcoma / enzymology
  • Sarcoma / genetics*
  • Sarcoma / pathology
  • Skin Neoplasms / enzymology
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / pathology
  • Telomerase / genetics*
  • Xanthomatosis / enzymology
  • Xanthomatosis / genetics*
  • Xanthomatosis / pathology


  • TERT protein, human
  • Telomerase