{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T10:05:40Z","timestamp":1792663540502,"version":"4.5.0"},"reference-count":43,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,2,7]],"date-time":"2023-02-07T00:00:00Z","timestamp":1675728000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005090","name":"Beijing Nova Program","doi-asserted-by":"publisher","award":["Z201100006820118"],"award-info":[{"award-number":["Z201100006820118"]}],"id":[{"id":"10.13039\/501100005090","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81903078"],"award-info":[{"award-number":["81903078"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82172783"],"award-info":[{"award-number":["82172783"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain Pathology"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    H3 K27\u2010altered diffuse midline glioma is a highly lethal pediatric\u2010type tumor without efficacious treatments. Recent findings have highlighted the heterogeneity among diffuse midline gliomas with different locations and ages. Compared to tumors located in the brain stem and thalamus, the molecular and clinicopathological features of H3 K27\u2010altered spinal cord glioma are still largely elusive, thus hindering the accurate management of patients. Here we aimed to characterize the clinicopathological and molecular features of H3 K27M\u2010mutant spinal cord glioma in 77 consecutive cases. We found that the H3 K27M\u2010mutant spinal cord glioma, with a median age of 35\u2009years old, had a significantly better prognosis than H3 K27M\u2010mutant brain tumors. We noticed a molecular heterogeneity of H3 K27M\u2010mutant spinal cord astrocytoma via targeted sequencing with 34 cases.\n                    <jats:italic>TP53<\/jats:italic>\n                    mutation which occurred in 58.8% of cases is mutually exclusive with\n                    <jats:italic>PPM1D<\/jats:italic>\n                    (26%) and\n                    <jats:italic>NF1<\/jats:italic>\n                    (44%) mutations. The\n                    <jats:italic>TP53<\/jats:italic>\n                    \u2010mutant cases had a significantly higher number of copy number variants (CNV) and a marginally higher proportion of pediatric patients (age at diagnosis &lt;18\u2009years old,\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a00.056). Cox regression and Kaplan\u2013Meier curve analysis showed that the higher number of CNV events (\u22653), chromosome (Chr) 9p deletion, Chr 10p deletion,\n                    <jats:italic>ATRX<\/jats:italic>\n                    mutation,\n                    <jats:italic>CDK6<\/jats:italic>\n                    amplification, and retinoblastoma protein\u00a0(RB)\u00a0pathway alteration are associated with worse survival. Cox regression analysis with clinicopathological features showed that glioblastoma histological type and a high Ki\u201067 index (&gt;10%) are associated with a worse prognosis. Interestingly, the histological type, an independent prognostic factor in multivariate Cox regression, can also stratify molecular features of H3 K27M\u2010mutant spinal cord glioma, including the RB\u00a0pathway, KRAS\/PI3K pathway, and chromosome arms CNV. In conclusion, although all H3 K27M\u2010mutant spinal cord diffuse glioma were diagnosed as WHO Grade 4, the histological type, molecular features representing chromatin instability, and molecular alterations associated with accelerated cell proliferative activity should not be ignored in clinical management.\n                  <\/jats:p>","DOI":"10.1111\/bpa.13153","type":"journal-article","created":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T00:45:39Z","timestamp":1675817139000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Genomic profiling and prognostic factors of\n                    <scp>H3 K27M<\/scp>\n                    \u2010mutant spinal cord diffuse glioma"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3451-8871","authenticated-orcid":false,"given":"Rui\u2010Chao","family":"Chai","sequence":"first","affiliation":[{"name":"Department of Molecular Neuropathology, Beijing Neurosurgical Institute Capital Medical University  Beijing China"},{"name":"Department of Neuropathology, Beijing Neurosurgical Institute Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Molecular Neuropathology, Beijing Neurosurgical Institute Capital Medical University  Beijing China"},{"name":"Department of Neurosurgery, Beijing Tiantan Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song\u2010Yuan","family":"An","sequence":"additional","affiliation":[{"name":"Department of Molecular Neuropathology, Beijing Neurosurgical Institute Capital Medical University  Beijing China"},{"name":"Department of Neurosurgery, Beijing Tiantan Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Pang","sequence":"additional","affiliation":[{"name":"Department of Molecular Neuropathology, Beijing Neurosurgical Institute Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3596-163X","authenticated-orcid":false,"given":"Hui\u2010Yuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neuropathology, Beijing Neurosurgical Institute Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan\u2010Hua","family":"Mu","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biological Engineering The Hong Kong University of Science and Technology  Hong Kong SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke\u2010Nan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Molecular Neuropathology, Beijing Neurosurgical Institute Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao\u2010Wu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Beijing Tiantan Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Qing","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Molecular Neuropathology, Beijing Neurosurgical Institute Capital Medical University  Beijing China"},{"name":"Department of Neuropathology, Beijing Neurosurgical Institute Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neuropathology, Beijing Neurosurgical Institute Capital Medical University  Beijing 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