%0 Journal Article
%A Koelsche, Christian
%A Stichel, Damian
%A Griewank, Klaus G
%A Schrimpf, Daniel
%A Reuss, David E
%A Bewerunge-Hudler, Melanie
%A Vokuhl, Christian
%A Dinjens, Winand N M
%A Petersen, Iver
%A Mittelbronn, Michel
%A Cuevas-Bourdier, Adrian
%A Buslei, Rolf
%A Pfister, Stefan
%A Flucke, Uta
%A Mechtersheimer, Gunhild
%A Mentzel, Thomas
%A von Deimling, Andreas
%T Genome-wide methylation profiling and copy number analysis in atypical fibroxanthomas and pleomorphic dermal sarcomas indicate a similar molecular phenotype.
%J Clinical Sarcoma Research
%V 9
%N 1
%@ 2045-3329
%C London
%I BioMed Central
%M DKFZ-2019-01079
%P 2
%D 2019
%X Atypical fibroxanthomas (AFX) and pleomorphic dermal sarcomas (PDS) are lesions of the skin with overlapping histologic features and unspecific molecular traits. PDS behaves aggressive compared to AFX. Thus, a precise delineation, although challenging in some instances, is relevant.We examined the value of DNA-methylation profiling and copy number analysis for separating these tumors. DNA-methylation data were generated from 17 AFX and 15 PDS using the Illumina EPIC array. These were compared with DNA-methylation data generated from 196 tumors encompassing potential histologic mimics like cutaneous squamous carcinomas (cSCC; n = 19), basal cell carcinomas (n = 10), melanoma metastases originating from the skin (n = 11), leiomyosarcomas (n = 11), angiosarcomas of the skin and soft tissue (n = 11), malignant peripheral nerve sheath tumors (n = 19), dermatofibrosarcomas protuberans (n = 13), extraskeletal myxoid chondrosarcomas (n = 9), myxoid liposarcomas (n = 14), schwannomas (n = 10), neurofibromas (n = 21), alveolar (n = 19) and embryonal (n = 17) rhabdomyosarcomas as well as undifferentiated pleomorphic sarcomas (n = 12).DNA-methylation profiling did not separate AFX from PDS. The DNA-methylation profiles of the other cases, however, were distinct from AFX/PDS. They reliably assigned to subtype-specific DNA-methylation clusters, although overlap occurred between some AFX/PDS and cSCC. Copy number profiling revealed alterations in a similar frequency and distribution between AFX and PDS. They involved losses of 9p (22/32) and 13q (25/32). Gains frequently involved 8q (8/32). Notably, a homozygous deletion of CDKN2A was more frequent in PDS (6/15) than in AFX (2/17), whereas amplifications were non-recurrent and overall rare (5/32).Our findings support the concept that AFX and PDS belong to a common tumor spectrum. We could demonstrate the diagnostic value of DNA-methylation profiling to delineating AFX/PDS from potential mimics. However, the assessment of certain histologic features remains crucial for separating PDS from AFX.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:30809375
%2 pmc:PMC6375211
%R 10.1186/s13569-019-0113-6
%U https://inrepo02.dkfz.de/record/143492