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@ARTICLE{Hench:275613,
author = {J. Hench and D. Mihic-Probst and A. Agaimy and S. Frank and
P. Meyer and C. Hultschig and S. Simi and L. Alos and T.
Balamurugan and W. Blokx and F. Bosisio and R. Cappellesso
and K. Griewank$^*$ and E. Hadaschik$^*$ and L. C. van
Kempen and W. Kempf and M. Lentini and L. Mazzucchelli and
G. Rinaldi and P. Rutkowski and D. Schadendorf$^*$ and B.
Schilling and A. Szumera-Cieckiewicz and J. van den Oord and
M. Mandalà and D. Massi},
collaboration = {E. M. Group},
title = {{C}linical, histopathological and molecular features of
dedifferentiated melanomas: {A}n {EORTC} {M}elanoma {G}roup
{R}etrospective {A}nalysis.},
journal = {European journal of cancer},
volume = {187},
issn = {0014-2964},
address = {Amsterdam [u.a.]},
publisher = {Elsevier},
reportid = {DKFZ-2023-00819},
pages = {7 - 14},
year = {2023},
abstract = {Dedifferentiated melanoma (DedM) poses significant
diagnostic challenges. We aimed to investigate the clinical,
histopathological and molecular features of DedM.
Methylation signature (MS) and copy number profiling (CNP)
were carried out in a subgroup of cases.A retrospective
series of 78 DedM tissue samples from 61 patients retrieved
from EORTC (European Organisation for Research and Treatment
of Cancer) Melanoma Group centres were centrally reviewed.
Clinical and histopathological features were retrieved. In a
subgroup of patients, genotyping through Infinium
Methylation microarray and CNP analysis was carried out.Most
patients (60/61) had a metastatic DedM showing most
frequently an unclassified pleomorphic, spindle cell, or
small round cell morphology akin to undifferentiated soft
tissue sarcoma, rarely associated with heterologous
elements. Overall, among 20 successfully analysed tissue
samples from 16 patients, we found retained melanoma-like MS
in only 7 tissue samples while a non-melanoma-like MS was
observed in 13 tissue samples. In two patients from whom
multiple specimens were analysed, some of the samples had a
preserved cutaneous melanoma MS while other specimens
exhibited an epigenetic shift towards a
mesenchymal/sarcoma-like profile, matching the histological
features. In these two patients, CNP was largely identical
across all analysed specimens, in line with their common
clonal origin, despite significant modification of their
epigenome.Our study further highlights that DedM represents
a real diagnostic challenge. While MS and genomic CNP may
help pathologists to diagnose DedM, we provide
proof-of-concept that dedifferentiation in melanoma is
frequently associated with epigenetic modifications.},
keywords = {Copy number profiling (Other) / DNA methylation (Other) /
Dedifferentiated melanoma (Other) / Epigenetics (Other)},
cin = {ED01},
ddc = {610},
cid = {I:(DE-He78)ED01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37098294},
doi = {10.1016/j.ejca.2023.03.032},
url = {https://inrepo02.dkfz.de/record/275613},
}