eprintid: 26109 rev_number: 14 eprint_status: archive userid: 1589 dir: disk0/00/02/61/09 datestamp: 2019-04-05 12:49:59 lastmod: 2024-05-13 05:15:25 status_changed: 2019-04-05 12:49:59 type: article metadata_visibility: show creators_name: Koelsche, Christian creators_name: Stichel, Damian creators_name: Griewank, Klaus G. creators_name: Schrimpf, Daniel creators_name: Reuss, David E. creators_name: Bewerunge‑Hudler, Melanie creators_name: Vokuhl, Christian creators_name: Dinjens, Winand N. M. creators_name: Petersen, Iver creators_name: Mittelbronn, Michel creators_name: Cuevas‑Bourdier, Adrian creators_name: Buslei, Rolf creators_name: Pfister, Stefan M. creators_name: Flucke, Uta creators_name: Mechtersheimer, Gunhild creators_name: Mentzel, Thomas creators_name: von Deimling, Andreas title: Genome-wide methylation profiling and copy number analysis in atypical fibroxanthomas and pleomorphic dermal sarcomas indicate a similar molecular phenotype divisions: i-850300 divisions: i-911600 divisions: i-912000 keywords: Pleomorphic dermal sarcoma, Atypical fibroxanthoma, Sarcomas, Melanomas, Carcinomas, Mimics, DNA methylation, Profiling abstract: Background: 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. Methods: 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). Results: 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). Conclusions: 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. date: 2019 publisher: BioMed Central id_scheme: DOI ppn_swb: 1665362391 own_urn: urn:nbn:de:bsz:16-heidok-261094 language: eng bibsort: KOELSCHECHGENOMEWIDE2019 full_text_status: public publication: Clinical Sarcoma Research volume: 9 number: 2 place_of_pub: London pagerange: 1-8 issn: 2045-3329 citation: Koelsche, Christian ; Stichel, Damian ; Griewank, Klaus G. ; Schrimpf, Daniel ; Reuss, David E. ; Bewerunge‑Hudler, Melanie ; Vokuhl, Christian ; Dinjens, Winand N. M. ; Petersen, Iver ; Mittelbronn, Michel ; Cuevas‑Bourdier, Adrian ; Buslei, Rolf ; Pfister, Stefan M. ; Flucke, Uta ; Mechtersheimer, Gunhild ; Mentzel, Thomas ; von Deimling, Andreas (2019) Genome-wide methylation profiling and copy number analysis in atypical fibroxanthomas and pleomorphic dermal sarcomas indicate a similar molecular phenotype. Clinical Sarcoma Research, 9 (2). pp. 1-8. ISSN 2045-3329 document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/26109/1/13569_2019_Article_113.pdf