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Integrative Analysis of Pleomorphic Dermal Sarcomas Reveals Fibroblastic Differentiation and Susceptibility to

Sebastian Klein1,2, Alexander Quaas3, Ka-Won Noh3

  • 1Institute for Pathology, University Hospital Cologne, Cologne, Germany. mpeifer@uni-koeln.de sebastian.klein@uk-koeln.de doris.helbig@uk-koeln.de.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|August 21, 2020
PubMed
Abstract

Insights

Pleomorphic dermal sarcoma (PDS) is a rare skin cancer of fibroblastic origin. This study reveals PDS has a high mutation rate and inflamed tumor microenvironment, suggesting susceptibility to immunotherapy.

Area of Science:

  • Oncology
  • Dermatology
  • Genomics

Background:

  • Pleomorphic dermal sarcoma (PDS) is a rare malignant cutaneous tumor with an unclear cell of origin.
  • Advanced PDS is challenging to treat with standard regimens.

Purpose of the Study:

  • To investigate the molecular characteristics and cell of origin of Pleomorphic dermal sarcoma (PDS).
  • To assess the potential of immunotherapy for treating PDS.

Main Methods:

  • Whole-exome sequencing on 28 individuals.
  • Transcriptomic analysis on 21 patients.
  • Quantitative immunohistochemistry (IHC) image analysis on 27 patients.

Main Results:

  • PDS exhibits a high mutational load (42.7 mutations/megabase) and an inflamed, immunogenic tumor microenvironment.
  • Three PDS cases responded to immune checkpoint blockade.
  • PDS is confirmed to be of mesenchymal, fibroblastic differentiation, with PDGFRB as a lineage marker.

Conclusions:

  • Pleomorphic dermal sarcoma (PDS) is a distinct entity of fibroblastic origin.
  • PDS demonstrates high susceptibility to immunotherapy due to its high mutational burden and inflamed tumor microenvironment.

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