Dataset Information

Primary spinal intradural mesenchymal chondrosarcoma with detection of fusion gene HEY1-NCOA2: A paediatric case report and review of the literature.

ABSTRACT: Mesenchymal chondrosarcoma is an extremely rare malignant tumour that most commonly originates in the bone, but is also present in extraskeletal sites. The tumour is morphologically characterized by a biphasic pattern of small round cells and islands of cartilage. Spinal mesenchymal chondrosarcomas are even rarer and, therefore, few investigations exist regarding the biological behaviour of the tumours. In the present study, we report a case of a 10-year-old female presenting with 9 months of back pain and radiographic findings of an intradural lesion measuring 1.5 cm at the level of Th4. The tumour was completely excised and subjected to pathological analyses. Following detection of the HEY1-NCOA2 fusion gene, the tumour was morphologically and immunohistochemically defined as an intradural mesenchymal chondrosarcoma attached to the dura mater. In this study, we validate the recent identification of the fusion gene HEY1-NCOA2 in paediatric extraskeletal mesenchymal chondrosarcomas. The relevant literature is reviewed and further discussed in relation to our findings.

SUBMITTER: Andersson C

PROVIDER: S-EPMC4156271 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Primary spinal intradural mesenchymal chondrosarcoma with detection of fusion gene HEY1-NCOA2: A paediatric case report and review of the literature.

Andersson Carola C Osterlundh Gustaf G Enlund Fredrik F Kindblom Lars-Gunnar LG Hansson Magnus M

Oncology letters 20140718 4

Mesenchymal chondrosarcoma is an extremely rare malignant tumour that most commonly originates in the bone, but is also present in extraskeletal sites. The tumour is morphologically characterized by a biphasic pattern of small round cells and islands of cartilage. Spinal mesenchymal chondrosarcomas are even rarer and, therefore, few investigations exist regarding the biological behaviour of the tumours. In the present study, we report a case of a 10-year-old female presenting with 9 months of ba ...[more]

PMID: 25202377

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Project description:Mesenchymal chondrosarcoma is a rare and often aggressive cancer that accounts for 2-10% of all chondrosarcomas. Genetically, this tumor is characterized by the recurrent HEY1-NCOA2 fusion. However, the oncogenic function of HEY1-NCOA2 fusion in mesenchymal chondrosarcoma remains to be elucidated. We stably transduced HEK293 as well as iPSC-derived mesenchymal stem cells (MSCs) with inducible- expression HEY1, NCOA2 and HEY1-NCOA2 construct, respectively. Using the stably transduced cell lines, we investigated the intracellular localization of HEY1-NCOA2 fusion protein and performed genome-wide chromatin Immunoprecipitation sequencing (ChIP-seq) and expression profiling (RNA-seq) to identify HEY1-NCOA2-dependent transcriptional regulation. In this study, HEY1-NCOA2 fusion protein was found to be localized to the nucleus, like wild-type HEY1; and extreme similarity in genome-wide DNA-binding pattern between HEY1-NCOA2 and wild-type HEY1 was observed. By gene expression profiling, HEY1-NCOA2-expression (MSC-HN+), HEY1-expression (MSC-HEY1+) and NCOA2-expression (MSC-NCOA2+) iPSC-MSCs can be robustly separated, and the combined differential gene expression (DGE) analysis and Gene Set Enrichment Analysis (GSEA) revealed that genes downregulated by HEY1 were positively enriched in MSC-HN+ versus control. Functional classification of HEY1-NCOA2 upregulated genes according to KEGG networks highlighted various pathways related to promoting cell proliferation in cancer, such as cell cycle pathway, Hedgehog and WNT signaling as well as PI3K-Akt signaling pathways. Indeed, MSC-HN+ cells displayed significantly accelerated proliferation and a significant increase in cell cycle transit when compared with control cells. In 3D spheroidal growth model, we also observed both accelerated cell proliferation and distinct morphological features of the MSC-HN+ cells in contrast to the control cells. Our data provide functional evidence that HEY1-NCOA2 fusion protein preferentially binds to DNA regions that are originally occupied by the wild-type HEY1 transcription factor, and the expression of some HEY1 target genes as well as their related pathways, that are normally repressed by HEY1, are activated in the presence of HEY1-NCOA2 fusion protein.

Dataset Information

Primary spinal intradural mesenchymal chondrosarcoma with detection of fusion gene HEY1-NCOA2: A paediatric case report and review of the literature.

Publications

Primary spinal intradural mesenchymal chondrosarcoma with detection of fusion gene HEY1-NCOA2: A paediatric case report and review of the literature.

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