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@ARTICLE{Kommoss:154658,
author = {F. K. Kommoss and K. T. Chang and D. Stichel$^*$ and A.
Banito$^*$ and D. Jones$^*$ and C. Heilig$^*$ and S.
Fröhling$^*$ and F. Sahm$^*$ and A. Stenzinger and W.
Hartmann and G. Mechtersheimer and H.-P. Sinn and D. Schmidt
and F. K. Kommoss$^*$ and A. von Deimling$^*$ and C.
Koelsche},
title = {{E}ndometrial stromal sarcomas with {BCOR}-rearrangement
harbor {MDM}2 amplifications.},
journal = {The journal of pathology: clinical research},
volume = {6},
number = {3},
issn = {2056-4538},
address = {Chichester},
publisher = {Wiley},
reportid = {DKFZ-2020-00919},
pages = {178-184},
year = {2020},
note = {2020 Jul;6(3):178-184 / #LA:B300#},
abstract = {Recently a novel subtype of endometrial stromal sarcoma
(ESS) defined by recurrent genomic alterations involving
BCOR has been described (HGESS-BCOR). We identified a case
of HGESS-BCOR with a ZC3H7B-BCOR gene fusion, which harbored
an amplification of the MDM2 locus. This index case prompted
us to investigate MDM2 amplification in four additional
cases of HGESS-BCOR. Tumors were analyzed for MDM2
amplification by array-based profiling of copy number
alterations (CNAs) and fluorescence in situ hybridization
(FISH), as well as for MDM2 expression by
immunohistochemistry (IHC). Additionally, a cohort of other
mesenchymal uterine neoplasms, including 17 low-grade ESS, 6
classical high-grade ESS with YWHAE-rearrangement, 16
uterine tumors resembling ovarian sex cord tumors, 7 uterine
leiomyomas and 8 uterine leiomyosarcomas, was analyzed for
CNAs in MDM2. Copy number profiling identified amplification
of the 12q15 region involving the MDM2 locus in all five
HGESS-BCOR. Subsequent validation analyses of three tumors
confirmed MDM2 amplification using MDM2 FISH. Accordingly,
IHC showed MDM2 overexpression in all analyzed cases. None
of the other uterine neoplasms in our series, including
tumors that are in the histopathological differential
diagnoses of HGESS-BCOR, showed copy number gains of MDM2.
Together, our results indicate that HGESS-BCOR carries MDM2
amplifications, which has diagnostic implications and could
potentially be used for targeted therapies in these
clinically aggressive tumors.},
cin = {HD01 / B300 / B380 / B360 / B340},
ddc = {610},
cid = {I:(DE-He78)HD01-20160331 / I:(DE-He78)B300-20160331 /
I:(DE-He78)B380-20160331 / I:(DE-He78)B360-20160331 /
I:(DE-He78)B340-20160331},
pnm = {312 - Functional and structural genomics (POF3-312)},
pid = {G:(DE-HGF)POF3-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:32352245},
doi = {10.1002/cjp2.165},
url = {https://inrepo02.dkfz.de/record/154658},
}