Copy number variations in atypical fibroxanthomas and pleomorphic dermal sarcomas

// Doris Helbig 1 , Alexander Quaas 2 , Cornelia Mauch 1 , Sabine Merkelbach-Bruse 2 , Reinhard Buttner 2 , Michael Emberger 3 , Marion Wobser 4 , Vanessa Russeler 2 , Katharina Putz 2 , Elke Binot 2 , Jan Rehker 2 , Jan Budczies 5 and Michaela Angelika Ihle 2 1 Department of Dermatology, University Hospital Cologne, Cologne, Germany 2 Institute of Pathology, University Hospital Cologne, Cologne, Germany 3 Institute of Pathology, Salzburg, Austria 4 Department of Dermatology, University Hospital Wurzburg, Wurzburg, Germany 5 Institute of Pathology, Charite University Hospital, Berlin, Germany Correspondence to: Doris Helbig, email: doris.helbig@uk-koeln.de Keywords: atypical fibroxanthoma; BRAF; copy number variation; pleomorphic dermal sarcoma Received: October 19, 2017      Accepted: November 13, 2017      Published: November 25, 2017 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.