Universität zu Köln

Klein, Sebastian ORCID: 0000-0002-2188-9377, Quaas, Alexander, Noh, Ka-Won, Cartolano, Maria, Abedpour, Nima, Mauch, Cornelia, Quantius, Jennifer, Reinhardt, Hans Christian, Buettner, Reinhard, Peifer, Martin and Helbig, Doris (2020). Integrative Analysis of Pleomorphic Dermal Sarcomas Reveals Fibroblastic Differentiation and Susceptibility to Immunotherapy. Clin. Cancer Res., 26 (21). S. 5638 - 5646. PHILADELPHIA: AMER ASSOC CANCER RESEARCH. ISSN 1557-3265

Full text not available from this repository.

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Klein, Sebastian UNSPECIFIED orcid.org/0000-0002-2188-9377 UNSPECIFIED Quaas, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Noh, Ka-Won UNSPECIFIED UNSPECIFIED UNSPECIFIED Cartolano, Maria UNSPECIFIED UNSPECIFIED UNSPECIFIED Abedpour, Nima UNSPECIFIED UNSPECIFIED UNSPECIFIED Mauch, Cornelia UNSPECIFIED UNSPECIFIED UNSPECIFIED Quantius, Jennifer UNSPECIFIED UNSPECIFIED UNSPECIFIED Reinhardt, Hans Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Buettner, Reinhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Peifer, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Helbig, Doris UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-313374
DOI:	10.1158/1078-0432.CCR-20-1899
Journal or Publication Title:	Clin. Cancer Res.
Volume:	26
Number:	21
Page Range:	S. 5638 - 5646
Date:	2020
Publisher:	AMER ASSOC CANCER RESEARCH
Place of Publication:	PHILADELPHIA
ISSN:	1557-3265
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SQUAMOUS-CELL CARCINOMA; DERMATOFIBROSARCOMA PROTUBERANS; MUTATIONAL LANDSCAPE; IMATINIB; CANCER; SIGNATURES; RESISTANT; BLOCKADE; FREQUENT; DEATH Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/31337