Recurrent non-canonical histone H3 mutations in spinal cord diffuse gliomas
Somatic mutations in the H3F3A and HIST1H3B genes encoding the histone H3 variants H3.3 and H3.1, respectively, are important genetic drivers of diffuse gliomas in both children and adults. The recurrent p.K27M mutation in either H3F3A or HIST1H3B genes is found in the majority of diffuse gliomas centered in midline structures of the central nervous system including the thalamus, brainstem, and spinal cord where it is associated with poor prognosis irrespective of histologic grade [9, 10, 11]. “Diffuse midline glioma, H3 K27M-mutant” was thus classified as a grade IV entity in the revised 2016 WHO Classification of Tumors of the Central Nervous System. In contrast, p.G34R or p.G34V mutation in the H3F3A gene is found in a subset of glioblastomas located in the cerebral hemispheres of adolescents and young adults and is associated with a more favorable prognosis [6, 8, 9, 10]. While the genetic landscape of supratentorial and brainstem gliomas has now been extensively characterized [9, 11...
We thank the staff of the UCSF Clinical Cancer Genomics Laboratory for assistance with genetic profiling. This study was supported in part by the UCSF Glioblastoma Precision Medicine Program. D.A.S. is supported by the NIH Director’s Early Independence Award (DP5 OD021403).
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Conflict of interest
The authors declare that they have no competing interests related to this report.
This study was approved by the Committee on Human Research of the University of California, San Francisco, with a waiver of patient consent.