Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Jul;6(3):178-184.
doi: 10.1002/cjp2.165. Epub 2020 Apr 30.

Endometrial stromal sarcomas with BCOR-rearrangement harbor MDM2 amplifications

Felix Kf Kommoss  1 , Kenneth Te Chang  2 , Damian Stichel  3   4 , Ana Banito  5   6 , David Tw Jones  5   7 , Christoph E Heilig  8   9 , Stefan Fröhling  8   9 , Felix Sahm  3   4 , Albrecht Stenzinger  1 , Wolfgang Hartmann  10 , Gunhild Mechtersheimer  1 , Hans-Peter Sinn  1 , Dietmar Schmidt  11 , Friedrich Kommoss  12 , Andreas von Deimling  3   4 , Christian Koelsche  1
Affiliations

Endometrial stromal sarcomas with BCOR-rearrangement harbor MDM2 amplifications

Felix Kf Kommoss et al. J Pathol Clin Res. 2020 Jul.

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.

Keywords: BCOR; MDM2; YWHAE; amplification; endometrial stromal sarcoma; neoplasm; uterine.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Histologic features of HGESS‐BCOR: sarcomatous proliferation of atypical and spindled neoplastic tumor cells with fascicular architecture (A and B), notable atypia (C) and prominent myxoid stroma (D). H&E stain; bar equals 50 μm.
Figure 2
Figure 2
MDM2 amplification in HGESS‐BCOR: (A) copy number profiles (cases 1–5). (B) MDM2 FISH (MDM2: green, CEN12: red) and immunohistochemical staining for MDM2 (cases 1–3). Bar equals 50 μm.
See this image and copyright information in PMC

References

    1. Hoang L, Chiang S, Lee CH. Endometrial stromal sarcomas and related neoplasms: new developments and diagnostic considerations. Pathology 2018; 50: 162–177. - PubMed
    1. Oliva E, Carcangiu ML, Carinelli S, et al Mesenchymal tumors In WHO Classification of Tumours of Female Reproductive Organs (4th edn), Kurman RJ, Carangiu ML, Herrington CS, et al (Eds). International Agency for Research on Cancer: Lyon, France, 2014; 135–147.
    1. Koontz JI, Soreng AL, Nucci M, et al Frequent fusion of the JAZF1 and JJAZ1 genes in endometrial stromal tumors. Proc Natl Acad Sci U S A 2001; 98: 6348–6353. - PMC - PubMed
    1. Halbwedl I, Ullmann R, Kremser ML, et al Chromosomal alterations in low‐grade endometrial stromal sarcoma and undifferentiated endometrial sarcoma as detected by comparative genomic hybridization. Gynecol Oncol 2005; 97: 582–587. - PubMed
    1. Lee CH, Ou WB, Marino‐Enriquez A, et al 14‐3‐3 fusion oncogenes in high‐grade endometrial stromal sarcoma. Proc Natl Acad Sci U S A 2012; 109: 929–934. - PMC - PubMed

Publication types

MeSH terms