Intracranial Mesenchymal Chondrosarcoma Lacking the Typical Histopathological Features Diagnosed by &lt;i&gt;HEY1-NCOA2&lt;/i&gt; Gene Fusion

Uneda, Atsuhito; Kurozumi, Kazuhiko; Fujimura, Akiko; Kamiya, Atsunori; Hirose, Takanori; Yanai, Hiroyuki; Date, Isao

doi:10.2176/nmccrj.cr.2019-0123

Cited by 7 publications

(4 citation statements)

References 21 publications

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“…The HEY1-NCOA2 fusion was identified as a recurrent fusion in mesenchymal chondrosarcoma by Wang et al in 2012 [5]. This fusion has been used successfully as a molecular marker for the diagnosis of mesenchymal chondrosarcoma [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. HEY1 (hairy/enhancer-of-split related with YRPW motif 1) is a member of the basic helix-loop-helix-orange (bHLH-O) family of transcriptional repressors and a downstream effector of Notch signaling [23].…”

Section: Introductionmentioning

confidence: 99%

Genomic profiling identifies genes and pathways dysregulated by HEY1–NCOA2 fusion and shines a light on mesenchymal chondrosarcoma tumorigenesis

Rosikiewicz

Yin

et al. 2022

The Journal of Pathology

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Mesenchymal chondrosarcoma is a rare, high‐grade, primitive mesenchymal tumor. It accounts for around 2–10% of all chondrosarcomas and mainly affects adolescents and young adults. We previously described the HEY1–NCOA2 as a recurrent gene fusion in mesenchymal chondrosarcoma, an important breakthrough for characterizing this disease; however, little study had been done to characterize the fusion protein functionally, in large part due to a lack of suitable models for evaluating the impact of HEY1–NCOA2 expression in the appropriate cellular context. We used iPSC‐derived mesenchymal stem cells (iPSC‐MSCs), which can differentiate into chondrocytes, and generated stable transduced iPSC‐MSCs with inducible expression of HEY1–NCOA2 fusion protein, wildtype HEY1 or wildtype NCOA2. We next comprehensively analyzed both the DNA binding properties and transcriptional impact of HEY1–NCOA2 expression by integrating genome‐wide chromatin immunoprecipitation sequencing (ChIP‐seq) and expression profiling (RNA‐seq). We demonstrated that HEY1–NCOA2 fusion protein preferentially binds to promoter regions of canonical HEY1 targets, resulting in transactivation of HEY1 targets, and significantly enhances cell proliferation. Intriguingly, we identified that both PDGFB and PDGFRA were directly targeted and upregulated by HEY1‐NCOA2; and the fusion protein, but not wildtype HEY1 or NCOA2, dramatically increased the level of phospho‐AKT (Ser473). Our findings provide a rationale for exploring PDGF/PI3K/AKT inhibition in treating mesenchymal chondrosarcoma. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

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Section: Introductionmentioning

confidence: 99%

Genomic profiling identifies genes and pathways dysregulated by HEY1–NCOA2 fusion and shines a light on mesenchymal chondrosarcoma tumorigenesis

Rosikiewicz

Yin

et al. 2022

The Journal of Pathology

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“…MCS cells are known to express mesenchymal markers. These include vimentin, CD99, B-cell lymphoma (BCL-2), and SRY-Box Transcription Factor 9 (SOX9) [ 23 , 26 ]. The expression of these markers and CD57 is detected in the small cells of many MCSs, while the S-100 protein is found in their cartilaginous regions [ 26 ].…”

Section: Chondrosarcoma Diagnosticsmentioning

confidence: 99%

“…Over the years, a fusion of the HEY1-NCOA2 gene has been successfully used as a molecular diagnostic marker for MCS, helping to diagnose cases lacking typical histological features [ 4 , 25 , 26 , 75 , 76 ]. Many studies suggest that tumors with nested round cell morphology and staghorn vasculature lacking a distinctive cartilaginous component should undergo FISH testing for HEY1-NCOA2 fusion [ 75 , 77 ].…”

Section: Genetic Alterations and Potential Targets For Novel Therapiesmentioning

confidence: 99%

Mesenchymal Chondrosarcoma from Diagnosis to Clinical Trials

Dudzisz-Śledź,

Kondracka,

Rudzińska

et al. 2023

Cancers

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Mesenchymal chondrosarcoma (MCS) is a rare subtype of chondrosarcoma with a poor prognosis. Although these tumors are sensitive to radiotherapy/chemotherapy, the standard treatment for localized MCS is only surgical resection, and there are no established treatment guidelines for patients with advanced and metastatic MCS. Due to the low incidence of MCS, the pathology of these tumors is still unknown, and other therapeutic options are lacking. Some studies show the potential role of the PDGF/PPI3K/AKT, PKC/RAF/MEK/ERK, and pRB pathways, and BCL2 overexpression in the pathogenesis of MCS. These findings provide an opportunity to use protein kinases and BCL2 inhibitors as potential therapy in MCS. In this review, we summarize the current knowledge about MCS diagnosis and treatment options. We show the immunological and molecular biomarkers used in the diagnosis of MCS. In addition, we discuss the known prognostic and predictive factors in MCS. Finally, we present the novel trends, including targeted therapies and ongoing clinical trials using protein kinase inhibitors and the death receptor 5 (DR5) agonist, which may be the focus of future MCS treatment studies.

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“…The median radiation dose was 50.2 Gy (30 Gy ~ 70.4 Gy; n = 10). Most patients received conventionally fractionated irradiation, but Gama-knife therapy [6,3,24,21,19,7,13] and proton beam therapy were also reported [21]. Patients with surgical extent and radiotherapy information were available in 90 cases, where neither GTR nor radiotherapy (NGnR) was found in 12 cases, GTR without radiotherapy in 30 cases, NGTR with radiotherapy in 20 cases, and GTR plus radiotherapy in 28 cases.…”

Section: Treatment Detailsmentioning

confidence: 99%

Active Treatment Strategy Improves Overall Survival of Patients With Intracranial Mesenchymal Chondrosarcoma After Surgical Treatment

Chen¹,

Chen²,

Hu³

et al. 2021

Preprint

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Intracranial mesenchymal chondrosarcoma (IMC) is a rare malignancy. We aimed to investigate the efficacy of treatment in overall survival (OS) for patients with IMC. Firstly, we retrospectively collected 9 cases from two medical centers, then screened the publications and enrolled 112 reported cases, and finally pooled these data together to analyze candidate prognostic factors for OS. For the treatment-related predictors, we defined active intervention if GTR (gross total resection) and/or radiotherapy (GaoR) was employed and inactive one when neither GTR nor radiotherapy (NGnR) was used. The 1-year, 3-year and 5-year OS for patients with IMC were 82.6%, 60.3% and 49.4%, respectively. NGnR was the independent risk factor for OS (HR [hazard ratio] = 4.70, 95% CI [confidence interval] 1.575 ~ 14.060; p = 0.006). The 1-year, 3-year and 5-year of patients with GaoR were higher than that of patients with NGnR (85.1%, 68.7% and 57.7% vs. 72.7%, 42.4% and 21.2%). Patients with IMC could obtain survival benefit from active intervention (GaoR group). GTR and/or radiotherapy should be recommended whenever feasible.

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Intracranial Mesenchymal Chondrosarcoma Lacking the Typical Histopathological Features Diagnosed by <i>HEY1-NCOA2</i> Gene Fusion

Cited by 7 publications

References 21 publications

Genomic profiling identifies genes and pathways dysregulated by HEY1–NCOA2 fusion and shines a light on mesenchymal chondrosarcoma tumorigenesis

Genomic profiling identifies genes and pathways dysregulated by HEY1–NCOA2 fusion and shines a light on mesenchymal chondrosarcoma tumorigenesis

Mesenchymal Chondrosarcoma from Diagnosis to Clinical Trials

Active Treatment Strategy Improves Overall Survival of Patients With Intracranial Mesenchymal Chondrosarcoma After Surgical Treatment

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