Case of the month 1-2019: CNS high-grade neuroepithelial tumor with BCOR alteration

Haberler, Christine; Reiniger, Lilla; Rajnai, Hajnalka; Kalev, Ognian; Gelpí, Ellen; Tamesberger, Melanie; Pietsch, Torsten

doi:10.5414/np301162

Cited by 13 publications

(21 citation statements)

References 18 publications

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“…Our results demonstrate that, similarly to previously described in CNS-HGNET with BCOR alteration 7 , 8 and CCSK, 6 soft tissue tumors with BCOR-ITD over expresses EGFR. The EGFR expression was strong and diffuse, membranous, and cytoplasmic, in the great majority of the tumors (8/9).…”

Section: Discussionsupporting

confidence: 90%

“…25 As previously described by Yoshida et al. 9 and others, 7 OLIG2 is positive in variable degrees in CNS HGNET with BCOR alterations. Yoshida et al.…”

Section: Discussionmentioning

confidence: 54%

“…4 All BCOR ITD-driven tumors share a similar histology and transcriptional signature, including overexpression of BCOR, cyclinD1, and BCL6, 5 which can be detected by immunohistochemistry. The CCSK 6 and CNS-HGNET 7,8 also show expression of epidermal growth factor receptor (EGFR). In 2018, Yoshida et al 9 compared by immunohistochemistry 6 cases of CNS HGNET with BCOR ITD with 5 cases of CCSK and only 1 PMMTI/URCS.…”

Section: Introductionmentioning

confidence: 99%

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Pediatric Soft Tissue Tumors With BCOR ITD Express EGFR but Not OLIG2

et al. 2020

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Introduction Somatic internal tandem duplication of 3’ of BCOR ( BCOR ITD) has been found in clear cell sarcomas of the kidney (CCSK), soft tissue undifferentiated round cell sarcomas/primitive myxoid mesenchymal tumors of infancy (URCS/PMMTI), and a subgroup of central nervous system high-grade neuroepithelial tumors (CNS-HGNET). BCOR ITD+ tumors share morphologic features. Expression of OLIG2 and epidermal growth factor receptor (EGFR) has been reported in CNS-HGNET with BCOR ITD. Here, we characterize OLIG2 and EGFR expression in URCS/PMMTI with BCOR ITD. Methods Paraffin blocks of 9 polymerase chain reaction-confirmed soft tissue BCOR ITD+ tumors (URCS/PMMTI) were immunophenotyped for OLIG2 and EGFR expression and scored semiquantitatively by percentage of positive cells and intensity of staining as negative, 1+, 2+, and 3+. Fluorescence in situ hybridization (FISH) for EGFR amplification was performed (amplification EGFR/CEP7 ratio ≥2.0). Results All 9 tumors showed membrane/cytoplasmic expression of EGFR, strong and diffuse (3+) in 8 cases; weak (+2) in 1. FISH detected no EGFR amplification. OLIG2 was negative in all. Conclusions EGFR is overexpressed in pediatric URCS/PMMTI with BCOR ITD and may be related to transcriptional upregulation of EGFR by BCOR ITD. OLIG2 negative staining differentiates URCS/PMMTI from CNS-HGNET. This finding may further support the possibility that these tumors have a different stem cell of origin.

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Section: Discussionsupporting

confidence: 90%

“…25 As previously described by Yoshida et al. 9 and others, 7 OLIG2 is positive in variable degrees in CNS HGNET with BCOR alterations. Yoshida et al.…”

Section: Discussionmentioning

confidence: 54%

Section: Introductionmentioning

confidence: 99%

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Pediatric Soft Tissue Tumors With BCOR ITD Express EGFR but Not OLIG2

et al. 2020

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“…Multi-gene detection method in this type of tumors can be supplemented by immunohistochemical analysis of BCOR protein. Nevertheless, BCOR can be also expressed in other brain tumors [1,4,5], especially in CNS HGNET-MN1, what is visible at the RNA level in our series as well (Fig. 1a).…”

Section: Discussionsupporting

confidence: 72%

Molecular identification of CNS NB-FOXR2, CNS EFT-CIC, CNS HGNET-MN1 and CNS HGNET-BCOR pediatric brain tumors using tumor-specific signature genes

Łastowska

Trubicka

Sobocińska

et al. 2020

acta neuropathol commun

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Four molecular types of rare central nervous system (CNS) tumors have been recently identified by gene methylation profiling: CNS Neuroblastoma with FOXR2 activation (CNS NB-FOXR2), CNS Ewing Sarcoma Family Tumor with CIC alteration (CNS EFT-CIC), CNS high grade neuroepithelial tumor with MN1 alteration (CNS HGNET-MN1) and CNS high grade neuroepithelial tumor with BCOR alteration (CNS HGNET-BCOR). Although they are not represented in 2016 updated WHO classification of CNS tumors, their diagnostic recognition is important because of clinical consequences. We have introduced a diagnostic method based on transcription profiling of tumor specific signature genes from formalin-fixed, paraffin-embedded tumor blocks using NanoString nCounter Technology. Altogether, 14 out of 187 (7.4%) high grade pediatric brain tumors were diagnosed with either of four new CNS categories. Histopathological examination of the tumors confirmed, that they demonstrate a spectrum of morphology mimicking other CNS high grade tumors. However, they also exhibit some suggestive histopathological and immunohistochemical features that allow for a presumptive diagnosis prior to molecular assessment. Clinical characteristics of patients corroborated with the previous findings for CNS EFT-CIC, CNS NB-FOXR2 and CNS HGNET-MN1 patients, with a favorable survival rate for the latter two groups. Among six CNS HGNE T-BCOR patients, three patients are long term survivors, suggesting possible heterogeneity within this molecular category of tumors. In summary, we confirmed the effectiveness of NanoString method using a single, multi-gene tumor specific signature and recommend this novel approach for identification of either one of the four newly described CNS tumor entities.

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“…This combination led to a sustained complete remission for 7.5 years and the patient is alive more than 10 years after initial diagnosis. Remission and survival are much longer than of most previously reported cases (Table S1) 1‐2,5‐11 . However, since this is a novel entity, the follow up for most of these cases is short.…”

Section: Discussionmentioning

confidence: 72%

A single supratentorial high‐grade neuroepithelial tumor with two distinct BCOR mutations, exceptionally long complete remission and survival

Bremer

Kottke

Johann

et al. 2020

Pediatric Blood & Cancer

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Here, we present a patient with high-grade neuroepithelial tumors with mutations in the BCL6 corepressor BCOR (HGNET-BCOR), a rare, highly malignant brain tumor with poor prognosis. The patient underwent gross total tumor resection (GTR), high-dose chemotherapy, and, after local relapse, GTR, proton radiation, and chemotherapy. After a 7.5 year-long complete remission, the tumor recurred locally, was treated by GTR, and responded to temozolomide treatment. In addition to an internal tandem duplication in BCOR common to the majority of HGNET-BCOR cases, molecular analysis revealed a second BCOR mutation in this tumor: a frame shift mutation. The combination of these mutations was associated with relatively low BCOR expression compared to other HGNET-BCOR cases.

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Case of the month 1-2019: CNS high-grade neuroepithelial tumor with BCOR alteration

Abstract: No abstract available.

Cited by 13 publications

References 18 publications

Pediatric Soft Tissue Tumors With BCOR ITD Express EGFR but Not OLIG2

Pediatric Soft Tissue Tumors With BCOR ITD Express EGFR but Not OLIG2

Molecular identification of CNS NB-FOXR2, CNS EFT-CIC, CNS HGNET-MN1 and CNS HGNET-BCOR pediatric brain tumors using tumor-specific signature genes

A single supratentorial high‐grade neuroepithelial tumor with two distinct BCOR mutations, exceptionally long complete remission and survival

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