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Integrative Analysis of Pleomorphic Dermal Sarcomas Reveals Fibroblastic Differentiation and Susceptibility to Immunotherapy.
Klein, Sebastian; Quaas, Alexander; Noh, Ka-Won; Cartolano, Maria; Abedpour, Nima; Mauch, Cornelia; Quantius, Jennifer; Reinhardt, Hans Christian; Buettner, Reinhard; Peifer, Martin; Helbig, Doris.
Afiliación
  • Klein S; Institute for Pathology, University Hospital Cologne, Cologne, Germany. mpeifer@uni-koeln.de sebastian.klein@uk-koeln.de doris.helbig@uk-koeln.de.
  • Quaas A; Else Kröner Forschungskolleg Clonal Evolution in Cancer, University Hospital Cologne, Cologne, Germany.
  • Noh KW; Institute for Pathology, University Hospital Cologne, Cologne, Germany.
  • Cartolano M; Institute for Pathology, University Hospital Cologne, Cologne, Germany.
  • Abedpour N; Department of Translational Genomics, Center of Integrated Oncology Cologne-Bonn, Medical Faculty, University of Cologne, Cologne, Germany.
  • Mauch C; Center for Molecular Medicine, Medical Faculty, University Hospital Cologne, Cologne, Germany.
  • Quantius J; Department of Translational Genomics, Center of Integrated Oncology Cologne-Bonn, Medical Faculty, University of Cologne, Cologne, Germany.
  • Reinhardt HC; Center for Molecular Medicine, Medical Faculty, University Hospital Cologne, Cologne, Germany.
  • Buettner R; Department of Dermatology, University Hospital Cologne, Cologne, Germany.
  • Peifer M; Institute for Pathology, University Hospital Cologne, Cologne, Germany.
  • Helbig D; Clinic for Hematology, West German Cancer Center, University Hospital Essen, Essen, German Cancer Consortium (DKTK), Germany.
Clin Cancer Res ; 26(21): 5638-5645, 2020 11 01.
Article en En | MEDLINE | ID: mdl-32817080
PURPOSE: Pleomorphic dermal sarcoma (PDS) is a rare malignant cutaneous tumor with an unknown cell of origin. Locally defined tumors can be treated by curative excisions, whereas advanced stages of the disease are difficult to treat, using standard regimens. EXPERIMENTAL DESIGN: We performed whole-exome sequencing on a cohort of 28 individuals and corresponding transcriptomic analysis on 21 patients, as well as quantitative IHC image analysis on 27 patients. RESULTS: PDS exhibits a universally high mutational load (42.7 mutations/mega base) with an inflamed, immunogenic tumor microenvironment. Three cases of PDS showed response to immune checkpoint blockade. Local mutation rate variation together with mRNA expression data demonstrate that PDS form a distinct entity, with PDGFRB as a lineage marker. In addition, we found that PDS is of mesenchymal, fibroblastic differentiation. CONCLUSIONS: PDS is of fibroblastic differentiation and exhibits a strong susceptibility to immunotherapy, including a high mutational burden and an inflamed tumor microenvironment.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sarcoma / Neoplasias Cutáneas / Transcriptoma / Inmunoterapia Límite: Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Clin Cancer Res Asunto de la revista: NEOPLASIAS Año: 2020 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sarcoma / Neoplasias Cutáneas / Transcriptoma / Inmunoterapia Límite: Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Clin Cancer Res Asunto de la revista: NEOPLASIAS Año: 2020 Tipo del documento: Article Pais de publicación: Estados Unidos