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Oncogene and therapeutic target analyses in atypical fibroxanthomas and pleomorphic dermal sarcomas

Doris Helbig1, Michaela Angelika Ihle2, Katharina Pütz2

  • 1Department of Dermatology, University Hospital Cologne, Cologne, Germany.

Oncotarget
|March 5, 2016
PubMed
Abstract

Insights

Atypical fibroxanthoma (AFX) may precede pleomorphic dermal sarcoma (PDS). Both tumor types share similar oncogene expression profiles and TP53 mutations, supporting AFX as a precursor lesion to PDS.

Area of Science:

  • Dermatopathology
  • Oncology
  • Molecular Biology

Background:

  • The tumorigenesis of atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) remains largely unknown.
  • A hypothesis suggests AFX is a non-infiltrating precursor to PDS.

Purpose of the Study:

  • To investigate the molecular and immunohistochemical characteristics of AFX and PDS.
  • To explore the potential precursor relationship between AFX and PDS.

Main Methods:

  • Comprehensive immunohistochemical and mutational analysis of AFX (n=5) and PDS (n=5) samples.
  • Next-generation sequencing (NGS) using a 17-hotspot gene panel.
  • Fluorescence in situ hybridization (FISH) for specific gene alterations.

Main Results:

  • TP53 mutations were detected in all PDS and the single analyzed AFX/PDS pair.
  • Mutations in CDKN2A, HRAS, KNSTRN, and PIK3CA were also identified.
  • Overexpression of TP53, CCND1, and CDK4 was observed in both AFX and PDS, with IMP3 upregulation in PDS.

Conclusions:

  • UV-induced TP53 mutations and CCND1/CDK4 alterations are crucial in PDS tumorigenesis.
  • Activating mutations in HRAS and PIK3CA were found in other oncogenic pathways.
  • Shared molecular profiles and mutations between AFX and PDS support the hypothesis of AFX as a precursor lesion.
Keywords:
CCND1CDK4TP53atypical fibroxanthomapleomorphic dermal sarcoma

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