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@ARTICLE{Kommoss:148317,
author = {F. K. F. Kommoss and D. Stichel$^*$ and D. Schrimpf$^*$ and
M. Kriegsmann and B. Tessier-Cloutier and A. Talhouk and J.
N. McAlpine and K. T. E. Chang and D. Sturm$^*$ and S. M.
Pfister$^*$ and L. Romero-Pérez and T. Kirchner and T. G.
P. Grünewald$^*$ and R. Buslei and H.-P. Sinn and G.
Mechtersheimer and P. Schirmacher and D. Schmidt and H.-A.
Lehr and F. Sahm and D. G. Huntsman and C. B. Gilks and F.
Kommoss and A. von Deimling$^*$ and C. Koelsche},
title = {{DNA} methylation-based profiling of uterine neoplasms: a
novel tool to improve gynecologic cancer diagnostics.213},
journal = {Journal of cancer research and clinical oncology},
volume = {146},
number = {1},
issn = {0171-5216},
address = {Berlin},
publisher = {Springer42162},
reportid = {DKFZ-2019-02875},
pages = {97-104},
year = {2020},
note = {2020 Jan;146(1):97-104 / #LA:B300#},
abstract = {Uterine neoplasms comprise a broad spectrum of lesions,
some of which may pose a diagnostic challenge even to
experienced pathologists. Recently, genome-wide DNA
methylation-based classification of central nervous system
tumors has been shown to increase diagnostic precision in
clinical practice when combined with standard
histopathology. In this study, we describe DNA methylation
patterns of a diverse set of uterine neoplasms and test the
applicability of array-based DNA methylation profiling.A
multicenter cohort including prototypical epithelial and
mesenchymal uterine neoplasms was collected. Tumors were
subject to pathology review and array-based DNA methylation
profiling (Illumina Infinium HumanMethylation450 or EPIC
[850k] BeadChip). Methylation data were analyzed by
unsupervised hierarchical clustering and t-SNE
analysis.After sample retrieval and pathology review the
study cohort consisted of 49 endometrial carcinomas (EC), 5
carcinosarcomas (MMMT), 8 uterine leiomyomas (ULMO), 7
uterine leiomyosarcomas (ULMS), 15 uterine tumor resembling
ovarian sex cord tumors (UTROSCT), 17 low-grade endometrial
stromal sarcomas (LGESS) and 9 high-grade endometrial
stromal sarcomas (HGESS). Analysis of methylation data
identified distinct methylation clusters, which correlated
with established diagnostic categories of uterine neoplasms.
MMMT clustered together with EC, while ULMO, ULMS and
UTROSCT each formed distinct clusters. The LGESS cluster
differed from that of HGESS, and within the branch of HGESS,
we observed a notable subgrouping of YWHAE- and
BCOR-rearranged tumors.Herein, we describe distinct DNA
methylation signatures in uterine neoplasms and show that
array-based DNA methylation analysis holds promise as an
ancillary tool to further characterize uterine neoplasms,
especially in cases which are diagnostically challenging by
conventional techniques.},
cin = {B300 / B062 / HD01},
ddc = {610},
cid = {I:(DE-He78)B300-20160331 / I:(DE-He78)B062-20160331 /
I:(DE-He78)HD01-20160331},
pnm = {312 - Functional and structural genomics (POF3-312)},
pid = {G:(DE-HGF)POF3-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:31768620},
doi = {10.1007/s00432-019-03093-w},
url = {https://inrepo02.dkfz.de/record/148317},
}