PMID- 32352245
OWN - NLM
STAT- MEDLINE
DCOM- 20210701
LR  - 20210701
IS  - 2056-4538 (Electronic)
IS  - 2056-4538 (Linking)
VI  - 6
IP  - 3
DP  - 2020 Jul
TI  - Endometrial stromal sarcomas with BCOR-rearrangement harbor MDM2 amplifications.
PG  - 178-184
LID - 10.1002/cjp2.165 [doi]
AB  - 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.
CI  - (c) 2020 The Authors. The Journal of Pathology: Clinical Research published by The 
      Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd.
FAU - Kommoss, Felix Kf
AU  - Kommoss FK
AUID- ORCID: 0000-0003-0876-9087
AD  - Department of Pathology, Institute of Pathology, Heidelberg University Hospital, 
      Heidelberg, Germany.
FAU - Chang, Kenneth Te
AU  - Chang KT
AD  - Department of Pathology and Laboratory Medicine, KK Women's and Children's 
      Hospital, Singapore, Singapore.
FAU - Stichel, Damian
AU  - Stichel D
AD  - Department of Neuropathology, Institute of Pathology, Heidelberg University 
      Hospital, Heidelberg, Germany.
AD  - Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German 
      Cancer Research Center (DKFZ), Heidelberg, Germany.
FAU - Banito, Ana
AU  - Banito A
AD  - Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
AD  - Pediatric Soft Tissue Sarcoma Research Group, German Cancer Research Center 
      (DKFZ), Heidelberg, Germany.
FAU - Jones, David Tw
AU  - Jones DT
AD  - Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
AD  - Pediatric Glioma Research Group, German Cancer Consortium (DKTK) and German 
      Cancer Research Center (DKFZ), Heidelberg, Germany.
FAU - Heilig, Christoph E
AU  - Heilig CE
AD  - German Cancer Consortium (DKTK), Heidelberg, Germany.
AD  - Division of Translational Medical Oncology, DKFZ and NCT Heidelberg, Heidelberg, 
      Germany.
FAU - Frohling, Stefan
AU  - Frohling S
AD  - German Cancer Consortium (DKTK), Heidelberg, Germany.
AD  - Division of Translational Medical Oncology, DKFZ and NCT Heidelberg, Heidelberg, 
      Germany.
FAU - Sahm, Felix
AU  - Sahm F
AD  - Department of Neuropathology, Institute of Pathology, Heidelberg University 
      Hospital, Heidelberg, Germany.
AD  - Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German 
      Cancer Research Center (DKFZ), Heidelberg, Germany.
FAU - Stenzinger, Albrecht
AU  - Stenzinger A
AD  - Department of Pathology, Institute of Pathology, Heidelberg University Hospital, 
      Heidelberg, Germany.
FAU - Hartmann, Wolfgang
AU  - Hartmann W
AUID- ORCID: 0000-0002-7609-5021
AD  - Division of Translational Pathology, Gerhard Domagk Institute of Pathology, 
      University Hospital Munster, Munster, Germany.
FAU - Mechtersheimer, Gunhild
AU  - Mechtersheimer G
AD  - Department of Pathology, Institute of Pathology, Heidelberg University Hospital, 
      Heidelberg, Germany.
FAU - Sinn, Hans-Peter
AU  - Sinn HP
AD  - Department of Pathology, Institute of Pathology, Heidelberg University Hospital, 
      Heidelberg, Germany.
FAU - Schmidt, Dietmar
AU  - Schmidt D
AD  - MVZ fur Histologie, Zytologie und Molekulare Diagnostik Trier GmbH, Trier, 
      Germany.
FAU - Kommoss, Friedrich
AU  - Kommoss F
AD  - Institute of Pathology, Medizin Campus Bodensee, Friedrichshafen, Germany.
FAU - von Deimling, Andreas
AU  - von Deimling A
AD  - Department of Neuropathology, Institute of Pathology, Heidelberg University 
      Hospital, Heidelberg, Germany.
AD  - Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German 
      Cancer Research Center (DKFZ), Heidelberg, Germany.
FAU - Koelsche, Christian
AU  - Koelsche C
AD  - Department of Pathology, Institute of Pathology, Heidelberg University Hospital, 
      Heidelberg, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200430
PL  - England
TA  - J Pathol Clin Res
JT  - The journal of pathology. Clinical research
JID - 101658534
RN  - 0 (BCOR protein, human)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (Repressor Proteins)
RN  - 0 (ZC3H7B protein, human)
RN  - EC 2.3.2.27 (MDM2 protein, human)
RN  - EC 2.3.2.27 (Proto-Oncogene Proteins c-mdm2)
SB  - IM
MH  - Biomarkers, Tumor/genetics
MH  - Cohort Studies
MH  - Endometrial Neoplasms/diagnosis/genetics/pathology
MH  - Female
MH  - Gene Fusion
MH  - Gene Rearrangement
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Proto-Oncogene Proteins/*genetics
MH  - Proto-Oncogene Proteins c-mdm2/*genetics
MH  - RNA-Binding Proteins/genetics
MH  - Repressor Proteins/*genetics
MH  - Sarcoma, Endometrial Stromal/*genetics/pathology
MH  - *Uterine Neoplasms/diagnosis/genetics/pathology
PMC - PMC7339170
OTO - NOTNLM
OT  - BCOR
OT  - MDM2
OT  - YWHAE
OT  - amplification
OT  - endometrial stromal sarcoma
OT  - neoplasm
OT  - uterine
EDAT- 2020/05/01 06:00
MHDA- 2021/07/02 06:00
PMCR- 2020/04/30
CRDT- 2020/05/01 06:00
PHST- 2020/01/27 00:00 [received]
PHST- 2020/03/07 00:00 [revised]
PHST- 2020/03/12 00:00 [accepted]
PHST- 2020/05/01 06:00 [pubmed]
PHST- 2021/07/02 06:00 [medline]
PHST- 2020/05/01 06:00 [entrez]
PHST- 2020/04/30 00:00 [pmc-release]
AID - CJP2165 [pii]
AID - 10.1002/cjp2.165 [doi]
PST - ppublish
SO  - J Pathol Clin Res. 2020 Jul;6(3):178-184. doi: 10.1002/cjp2.165. Epub 2020 Apr 
      30.