A rare case of paediatric astroblastoma with concomitant MN1‐GTSE1 and EWSR1‐PATZ1 gene fusions altering management

Chadda, Karan R.; Holland, Katherine D.; Scoffings, Daniel; Dean, Andrew; Pickles, Jessica C.; Behjati, Sam; Jacques, Thomas S.; Trotman, Jamie; Tarpey, Patrick; Allinson, Kieren; Murray, Matthew J.

doi:10.1111/nan.12701

Cited by 15 publications

(9 citation statements)

References 25 publications

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“…The protein produced by the fusion of the N‐terminal domain of EWSR1 and the C‐terminal domain of other transcription factors is common in soft tissue sarcomas (e.g., Ewing sarcoma, small round‐cell tumor, myxoid liposarcoma, hemangioma‐like fibrous histiocytoma, and clear cell sarcoma) 4 . The fusion of EWSR1–PATZ1 and MN1–GTSE1 was reported in one case of pediatric astroblastoma, 2 and EWSR1–BEND2 fusion was detected in another case of astroblastoma in the spinal cord 1 . EWSR1–PATZ1 fusion has been detected in papillary glioneuronal tumors 5 ; however, currently there are no clinical reports on the EWSR1–EZHIP gene rearrangement in astroblastomas.…”

Section: Discussionmentioning

confidence: 99%

“…In conclusion, our patient had a tumor with typical astroblastoma morphology, with no MN1 alteration. According to the WHO classification diagnostic criteria for 2021, the lesion should be integrated and diagnosed as “astroblastoma, NEC.” Currently, 10 cases of astroblastoma with EWSR1 changes have been reported in the literature 1–3 . Some cases of methylation have been classified as MN1 changes in high‐grade neuroepithelial tumors of the central nervous system and others as PATZ1‐related neuroepithelial tumors 1–3 .…”

Section: Discussionmentioning

confidence: 99%

“…In addition, Chadda et al reported a rare case of pediatric astroblastoma with concomitant MN1–GTSE1 and EWSR1–PATZ1 fusions that required a specific management. The tumor methylation analysis showed clusters of neuroepithelial cells associated with the PATZ1 fusion 2 . Lucas et al reported eight cases of astroblastoma with EWSR1–BEND2 fusion 3 .…”

Section: Introductionmentioning

confidence: 99%

“…The tumor methylation analysis showed clusters of neuroepithelial cells associated with the PATZ1 fusion. 2 Lucas et al reported eight cases of astroblastoma with EWSR1-BEND2 fusion. 3 These three articles reported EWSR1 alterations and suggested that some astroblastomas may be related to EWSR1 fusion.…”

Section: Introductionmentioning

confidence: 99%

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An EWSR1–EZHIP fusion in a cerebral hemisphere astroblastoma

et al. 2023

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Astroblastomas are considered extremely rare tumors and have not been formally graded. While gene mutations are used to diagnose these tumors, further research is needed for proper diagnosis and classification. This report presents a case of astroblastoma in a 44-year-old woman. A tumor was found to have histology consistent with astroblastoma, with no MN1 gene changes. Several mutations were present, and fusion of the EWSR1 and EZHIP genes was noted, which has never been reported before in the literature. Fusions of the EWSR1 gene could be characteristics of astroblastomas, in addition to MN1 alterations, and identification of these mutations could help in the diagnosis of these rare tumors.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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An EWSR1–EZHIP fusion in a cerebral hemisphere astroblastoma

et al. 2023

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“…[10,35,36,43,57] and reviewed in [16]). Interestingly, recent reports have identified a handful of pediatric brain tumors displaying a fusion of the PATZ1 gene with either MN1 or EWSR1 as a partner [1,4,6,14,35,38,42,45] (summarized in Table 1, top panel). The histological diagnoses of these tumors included glial, glioneuronal and 'polyphenotypic' morphologies, hinting at some potential similarities but also variation in appearance, which may have prevented previous recognition as a defined entity.…”

Section: Introductionmentioning

confidence: 99%

PATZ1 fusions define a novel molecularly distinct neuroepithelial tumor entity with a broad histological spectrum

et al. 2021

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Large-scale molecular profiling studies in recent years have shown that central nervous system (CNS) tumors display a much greater heterogeneity in terms of molecularly distinct entities, cellular origins and genetic drivers than anticipated from histological assessment. DNA methylation profiling has emerged as a useful tool for robust tumor classification, providing new insights into these heterogeneous molecular classes. This is particularly true for rare CNS tumors with a broad morphological spectrum, which are not possible to assign as separate entities based on histological similarity alone. Here, we describe a molecularly distinct subset of predominantly pediatric CNS neoplasms (n = 60) that harbor PATZ1 fusions. The original histological diagnoses of these tumors covered a wide spectrum of tumor types and malignancy grades. While the single most common diagnosis was glioblastoma (GBM), clinical data of the PATZ1-fused tumors showed a better prognosis than typical GBM, despite frequent relapses. RNA sequencing revealed recurrent MN1:PATZ1 or EWSR1:PATZ1 fusions related to (often extensive) copy number variations on chromosome 22, where PATZ1 and the two fusion partners are located. These fusions have individually been reported in a number of glial/glioneuronal tumors, as well as extracranial sarcomas. We show here that they are more common than previously acknowledged, and together define a biologically distinct CNS tumor type with high expression of neural development markers such as PAX2, GATA2 and IGF2. Drug screening performed on the MN1:PATZ1 fusion-bearing KS-1 brain tumor cell line revealed preliminary candidates for further study. In summary, PATZ1 fusions define a molecular class of histologically polyphenotypic neuroepithelial tumors, which show an intermediate prognosis under current treatment regimens.

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