{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Histone H3C1 is one of the replication‐dependent “canonical” H3 variants that, together with other members of its family, plays a central role in packaging DNA into chromatin and in maintaining epigenetic states during cell division. In several pediatric brain tumors—most notably diffuse intrinsic pontine gliomas (DIPG) and other midline high‐grade gliomas—molecular analyses have uncovered distinct mutation patterns in histone H3 variants. In these tumors, oncogenic mutations that substitute lysine 27 with methionine (K27M) occur either in the replication‐independent H3.3 (encoded by H3F3A) or in the canonical H3.1 variants that include genes such as HIST1H3B and HIST1H3C. Notably, tumors harboring H3.1 K27M aberrations show a divergent molecular and clinical profile relative to their H3.3 counterparts; for instance, H3.1‐mutated tumors tend to exhibit a mesenchymal/astrocytic phenotype with pro‐angiogenic/hypoxic signatures, and they may respond differently to radiotherapy."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to mutation‐driven changes, epigenetic alterations of H3C1 itself can have prognostic significance. For example, aberrant methylation of the HIST1H3C promoter has been associated with established risk factors—such as patient age, disease stage, or MYCN status—in neuroblastoma, and increased HIST1H3C methylation correlates with poorer overall and event‐free survival. This supports a functional role for the epigenetic state of canonical H3 variants in regulating gene expression programs relevant to tumor behavior."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Together, these findings underscore the dual role of H3C1: as an essential structural component of chromatin that ensures proper replication‐dependent nucleosome assembly, and as a modifiable substrate whose alterations—whether by somatic mutation or by epigenetic mechanisms—can drive distinct oncogenic programs and serve as biomarkers for stratifying patient risk.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Dong-Anh Khuong-Quang, Pawel Buczkowicz, Patricia Rakopoulos, et al. "}, {"type": "b", "children": [{"type": "t", "text": "K27M mutation in histone H3.3 defines clinically and biologically distinct subgroups of pediatric diffuse intrinsic pontine gliomas."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Neuropathol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00401-012-0998-0"}], "href": "https://doi.org/10.1007/s00401-012-0998-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22661320"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22661320"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "David Castel, Cathy Philippe, Raphaël Calmon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Histone H3F3A and HIST1H3B K27M mutations define two subgroups of diffuse intrinsic pontine gliomas with different prognosis and phenotypes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Neuropathol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00401-015-1478-0"}], "href": "https://doi.org/10.1007/s00401-015-1478-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26399631"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26399631"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Adam M Fontebasso, Simon Papillon-Cavanagh, Jeremy Schwartzentruber, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Recurrent somatic mutations in ACVR1 in pediatric midline high-grade astrocytoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.2950"}], "href": "https://doi.org/10.1038/ng.2950"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24705250"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24705250"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Anneleen Decock, Maté Ongenaert, Jasmien Hoebeeck, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide promoter methylation analysis in neuroblastoma identifies prognostic methylation biomarkers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genome Biol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/gb-2012-13-10-r95"}], "href": "https://doi.org/10.1186/gb-2012-13-10-r95"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23034519"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23034519"}]}]}]}