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. 2017 Nov 25;8(65):109457-109467.
doi: 10.18632/oncotarget.22691. eCollection 2017 Dec 12.

Copy number variations in atypical fibroxanthomas and pleomorphic dermal sarcomas

Doris Helbig  1 , Alexander Quaas  2 , Cornelia Mauch  1 , Sabine Merkelbach-Bruse  2 , Reinhard Büttner  2 , Michael Emberger  3 , Marion Wobser  4 , Vanessa Rüsseler  2 , Katharina Pütz  2 , Elke Binot  2 , Jan Rehker  2 , Jan Budczies  5 , Michaela Angelika Ihle  2
Affiliations

Copy number variations in atypical fibroxanthomas and pleomorphic dermal sarcomas

Doris Helbig et al. Oncotarget. .

Abstract

Atypical fibroxanthomas (AFX) and pleomorphic dermal sarcomas (PDS) are frequent cutaneous sarcomas typically arising on sun-exposed skin in elderly patients. In contrast to AFX, which generally do not recur after complete excision, PDS locally recur in up to 50% and metastasize in up to 20%. We recently detected characteristic UV-induced TP53 mutations as potential driver mutation in almost all PDS investigated as well as activating PIK3CA and RAS gene mutations in around one third of our tumors representing targets for personalized treatments in patients with unresectable or metastasized PDS. In the present study, we identified amplifications and deletions in a small part of the PDS (6 of 27 cases) but not in AFX suggesting that copy number variations (CNV) might not be an initial event in tumor development but rather important during tumor progression. In addition to BRAF, KNSTRN, IDH1 and PDGFRA amplification, CNV analyses revealed deletions in the CDKN2A, KIT and PDGFRA genes. In cases where an appropriate FISH assay was established, the CNV results could be verified by FISH analysis. Amplification of BRAF, KIT or PDGFRA and/or losses of CDKN2A might represent bad prognostic markers, although larger studies are needed to clarify their association with prognosis or progression in PDS.

Keywords: BRAF; atypical fibroxanthoma; copy number variation; pleomorphic dermal sarcoma.

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Conflict of interest statement

CONFLICTS OF INTEREST There is no conflict of interest. The study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki as reflected by the approval of the institution’s human research review committee (registration no. 15-307). Informed consent has been obtained.

Figures

Figure 1
Figure 1. Copy number variation (CNV) in pleomorphic dermal sarcomas (PDS)
(A) Heatmap diagram of the CNVs in a melanoma specific gene panel detected by the software tool Ioncopy. Red indicates an amplification and green a deletion. (B) Verification of BRAF amplification by FISH analysis. (C) Verification of KIT deletion by FISH analysis. (D) Verification of PDGFRA amplification by FISH analysis. (E) Verification of PDGFRA deletion by FISH analysis.
Figure 2
Figure 2. Verification of negative case P6
Negative results by Ioncopy were verified by FISH analysis if an appropriate assay was available. (A, B) HE staining, (C) BRAF FISH, (D) CDK4 FISH, (E) KIT FISH, and (F) PDGFRA FISH.
See this image and copyright information in PMC

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