This article requires a subscription to view the full text. You may purchase access to this article or login to access your subscription using the links below.
Abstract
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
Footnotes
Note: Supplementary data for this article are available at Clinical Cancer Research Online (http://clincancerres.aacrjournals.org/).
Clin Cancer Res 2020;26:5638–45
- Received May 18, 2020.
- Revision received July 8, 2020.
- Accepted August 7, 2020.
- Published first August 17, 2020.
- ©2020 American Association for Cancer Research.
Log in using your username and password
Purchase access
Volume 26, Issue 21
