PT  - JOURNAL ARTICLE
AU  - Klein, Sebastian
AU  - Quaas, Alexander
AU  - Noh, Ka-Won
AU  - Cartolano, Maria
AU  - Abedpour, Nima
AU  - Mauch, Cornelia
AU  - Quantius, Jennifer
AU  - Reinhardt, Hans Christian
AU  - Buettner, Reinhard
AU  - Peifer, Martin
AU  - Helbig, Doris
TI  - Integrative Analysis of Pleomorphic Dermal Sarcomas Reveals Fibroblastic Differentiation and Susceptibility to Immunotherapy
AID  - 10.1158/1078-0432.CCR-20-1899
DP  - 2020 Nov 01
TA  - Clinical Cancer Research
PG  - 5638--5645
VI  - 26
IP  - 21
4099  - http://clincancerres.aacrjournals.org/content/26/21/5638.short
4100  - http://clincancerres.aacrjournals.org/content/26/21/5638.full
SO  - Clin Cancer Res2020 Nov 01; 26
AB  - 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.This article is featured in Highlights of This Issue, p. 5541