Atypical histone H3 mutation in spinal diffuse glioma

Backgroundcoding histoneH3 variants H3.3 and H3.1 Genes H3F3A and HIST1H3B gene somatic cell mutations are important genetic drivers of diffuse glioma in children and adultsThe p.K27M mutation in the H3F3A or HIST1H3B gene is found in most diffuse gliomasThese diffuse gliomas are concentrated in the middle-line structure of the central nervous system, including the thalamus, brain stem and spinal cord, and have poor prognosisTherefore, "midline glioma, H3 K27M mutant type" is classified as a grade IV solid tumor in the 2016 WHO Central Nervous System Tumor Classification RevisionAt present, the genetic characteristics of glioma and brain stem glioma have been extensively studied, but the genetic drivers of spinal cord diffuse glioma are little knownEmily ASloan, of the University of California, San Francisco (UCSF) Pathology Department, and others reported genomic characteristics of 13 cases of spinal diffuse glioma, identifying atypical histone H3 mutations, including H3F3A p.GG34W and H3F3B p.K27I mutationsThe results were published online in Acta Neuropathol in September 2019study methods
included 13 patients, including 10 males and 3 women, aged 4 to 71The tumor in the spinal myelin is concentrated in the chest 8, neck 4 and waist 1 sectionAll patients were subjected to a tissue biopsy or partial removal of the tumorThe microscope was diagnosed as diffuse astrocyte glioma based on histological characteristics, including 4 pervasive astrocymas, 4 cases of transsexual atom cell tumors and 5 cases of glioblastomathe results of the study
the authors used the UCSF500 Cancer Panel to target 13 tumors and sequence NGS In 13 cases, 11 had at least one histone H3 gene mutation P.K27M mutation in the H3F3A gene of 9 tumors (Figure 1a) In the H3F3A gene of 2 tumors, it has p G34W mutation; 1 case p The G34W mutation was found in hetin H3 p.K27M wild tumors, while the other case was on the same allele, the same as the H3F3A p.K27M mutation that occurred simultaneously (Figure 1b) The H3F3B gene in 1 case of H3F3A wild tumor had a p.K27I mutation, which encoded histone H3 variant H3.3, and had the same amino acid sequence as the protein product encoded by the H3F3A gene The H3F3B gene mutation in somatic cells in central nervous system tumors has not previously been reported The H3F3Bp.K36M mutation was found only in the vast majority of cartilage cell tumors The authors report the first case of histone H3 gene in diffuse midline glioma that carries a p.K27I mutation, a non-common p K27M mutation The main function of histone H3 gene p.K27M mutation is to prevent methylation on the tail residual spout of histone H3, thus blocking key modificationafters after translation and promoting transcriptional differentiation of glial cells Since isolenine is not methylated, this non-classical mutation is expected to be used to block methylation at the residual base To study the effects of this H3F3B p.K27I mutation, the researchers immunochemically dyed histone H3K27M trimethylation (H3K27me3) and found that H3K27me3 was lost in most tumor cell nuclei (Figure 1b) A Clinical pathological characteristics of atypical spinal lygo; b histological characteristics of imaging conclusions the above, the authors reported 13 cases of spinal diffuse glioma These gliomas contain recurrent, atypical histone H3 mutations, whose effects on clinical prognosis have yet to be determined The author believes that due to the lack of understanding of the immune reactive of H3 K27M mutant protein, it is not enough to classify spinal diffuse glioma as a wild type of histone H3, and it is necessary to consider other hetin H3 mutations of spinal diffuse glioma for corresponding molecular evaluation.