RT Journal Article
SR Electronic
T1 Integrative Analysis of Pleomorphic Dermal Sarcomas Reveals Fibroblastic Differentiation and Susceptibility to Immunotherapy
JF Clinical Cancer Research
JO Clin Cancer Res
FD American Association for Cancer Research
SP 5638
OP 5645
DO 10.1158/1078-0432.CCR-20-1899
VO 26
IS 21
A1 Klein, Sebastian
A1 Quaas, Alexander
A1 Noh, Ka-Won
A1 Cartolano, Maria
A1 Abedpour, Nima
A1 Mauch, Cornelia
A1 Quantius, Jennifer
A1 Reinhardt, Hans Christian
A1 Buettner, Reinhard
A1 Peifer, Martin
A1 Helbig, Doris
YR 2020
UL http://clincancerres.aacrjournals.org/content/26/21/5638.abstract
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