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@ARTICLE{Koelsche:143492,
author = {C. Koelsche and D. Stichel$^*$ and K. G. Griewank and D.
Schrimpf$^*$ and D. E. Reuss$^*$ and M. Bewerunge-Hudler$^*$
and C. Vokuhl and W. N. M. Dinjens and I. Petersen and M.
Mittelbronn and A. Cuevas-Bourdier and R. Buslei and S.
Pfister$^*$ and U. Flucke and G. Mechtersheimer and T.
Mentzel and A. von Deimling$^*$},
title = {{G}enome-wide methylation profiling and copy number
analysis in atypical fibroxanthomas and pleomorphic dermal
sarcomas indicate a similar molecular phenotype.},
journal = {Clinical Sarcoma Research},
volume = {9},
number = {1},
issn = {2045-3329},
address = {London},
publisher = {BioMed Central},
reportid = {DKFZ-2019-01079},
pages = {2},
year = {2019},
abstract = {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.},
cin = {B300 / W110 / B062},
ddc = {610},
cid = {I:(DE-He78)B300-20160331 / I:(DE-He78)W110-20160331 /
I:(DE-He78)B062-20160331},
pnm = {312 - Functional and structural genomics (POF3-312)},
pid = {G:(DE-HGF)POF3-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:30809375},
pmc = {pmc:PMC6375211},
doi = {10.1186/s13569-019-0113-6},
url = {https://inrepo02.dkfz.de/record/143492},
}