Hypermutated phenotype in gliosarcoma of the spinal cord
Abstract Gliosarcoma is a variant of glioblastoma with equally poor prognosis and characterized by mixed glial and mesenchymal pathology. Metastasis is not uncommon but the involvement of the spinal cord is rare, and comprehensive genetic characterization of spinal gliosarcoma is lacking. We describ...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2021-02-01
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| Series: | npj Precision Oncology |
| Online Access: | https://doi.org/10.1038/s41698-021-00143-w |
| _version_ | 1797421414299467776 |
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| author | Christopher S. Hong Gregory A. Kuzmik Adam J. Kundishora Aladine A. Elsamadicy Andrew B. Koo Declan McGuone Nicholas A. Blondin Michael L. DiLuna E. Zeynep Erson-Omay |
| author_facet | Christopher S. Hong Gregory A. Kuzmik Adam J. Kundishora Aladine A. Elsamadicy Andrew B. Koo Declan McGuone Nicholas A. Blondin Michael L. DiLuna E. Zeynep Erson-Omay |
| author_sort | Christopher S. Hong |
| collection | DOAJ |
| description | Abstract Gliosarcoma is a variant of glioblastoma with equally poor prognosis and characterized by mixed glial and mesenchymal pathology. Metastasis is not uncommon but the involvement of the spinal cord is rare, and comprehensive genetic characterization of spinal gliosarcoma is lacking. We describe a patient initially diagnosed with a low-grade brain glioma via biopsy, followed by adjuvant radiation and temozolomide treatment. Nearly 2 years after diagnosis, she developed neurological deficits from an intradural, extramedullary tumor anterior to the spinal cord at T4, which was resected and diagnosed as gliosarcoma. Whole-exome sequencing (WES) of this tumor revealed a hypermutated phenotype, characterized by somatic mutations in key DNA mismatch repair (MMR) pathway genes, an abundance of C>T transitions within the identified somatic single nucleotide variations, and microsatellite stability, together consistent with temozolomide-mediated hypermutagenesis. This is the first report of a hypermutator phenotype in gliosarcoma, which may represent a novel genomic mechanism of progression from lower grade glioma. |
| first_indexed | 2024-03-09T07:15:47Z |
| format | Article |
| id | doaj.art-a6a8850fbc314bbebd402b0441814fc4 |
| institution | Directory Open Access Journal |
| issn | 2397-768X |
| language | English |
| last_indexed | 2024-03-09T07:15:47Z |
| publishDate | 2021-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Precision Oncology |
| spelling | doaj.art-a6a8850fbc314bbebd402b0441814fc42023-12-03T08:32:45ZengNature Portfolionpj Precision Oncology2397-768X2021-02-01511610.1038/s41698-021-00143-wHypermutated phenotype in gliosarcoma of the spinal cordChristopher S. Hong0Gregory A. Kuzmik1Adam J. Kundishora2Aladine A. Elsamadicy3Andrew B. Koo4Declan McGuone5Nicholas A. Blondin6Michael L. DiLuna7E. Zeynep Erson-Omay8Department of Neurosurgery, Yale School of MedicineDepartment of Neurosurgery, Yale School of MedicineDepartment of Neurosurgery, Yale School of MedicineDepartment of Neurosurgery, Yale School of MedicineDepartment of Neurosurgery, Yale School of MedicineDepartment of Pathology, Yale School of MedicineDepartment of Neurology, Yale School of MedicineDepartment of Neurosurgery, Yale School of MedicineDepartment of Neurosurgery, Yale School of MedicineAbstract Gliosarcoma is a variant of glioblastoma with equally poor prognosis and characterized by mixed glial and mesenchymal pathology. Metastasis is not uncommon but the involvement of the spinal cord is rare, and comprehensive genetic characterization of spinal gliosarcoma is lacking. We describe a patient initially diagnosed with a low-grade brain glioma via biopsy, followed by adjuvant radiation and temozolomide treatment. Nearly 2 years after diagnosis, she developed neurological deficits from an intradural, extramedullary tumor anterior to the spinal cord at T4, which was resected and diagnosed as gliosarcoma. Whole-exome sequencing (WES) of this tumor revealed a hypermutated phenotype, characterized by somatic mutations in key DNA mismatch repair (MMR) pathway genes, an abundance of C>T transitions within the identified somatic single nucleotide variations, and microsatellite stability, together consistent with temozolomide-mediated hypermutagenesis. This is the first report of a hypermutator phenotype in gliosarcoma, which may represent a novel genomic mechanism of progression from lower grade glioma.https://doi.org/10.1038/s41698-021-00143-w |
| spellingShingle | Christopher S. Hong Gregory A. Kuzmik Adam J. Kundishora Aladine A. Elsamadicy Andrew B. Koo Declan McGuone Nicholas A. Blondin Michael L. DiLuna E. Zeynep Erson-Omay Hypermutated phenotype in gliosarcoma of the spinal cord npj Precision Oncology |
| title | Hypermutated phenotype in gliosarcoma of the spinal cord |
| title_full | Hypermutated phenotype in gliosarcoma of the spinal cord |
| title_fullStr | Hypermutated phenotype in gliosarcoma of the spinal cord |
| title_full_unstemmed | Hypermutated phenotype in gliosarcoma of the spinal cord |
| title_short | Hypermutated phenotype in gliosarcoma of the spinal cord |
| title_sort | hypermutated phenotype in gliosarcoma of the spinal cord |
| url | https://doi.org/10.1038/s41698-021-00143-w |
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