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| ===Additional Description:=== | | ===Additional Description:=== |
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| + | Mutually exclusive: IDH1 mutation, EGFR amplification |
| + | Rare co-occurrence: BRAF V600E |
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| ==Gene Mutations (SNV/INDEL)== | | ==Gene Mutations (SNV/INDEL)== |
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| ==Epigenomics (Methylation)== | | ==Epigenomics (Methylation)== |
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| + | The lysine 27 to methionine substitution in histone variant H3.3 (H3.3-K27M) mutation leads to a global reduction of H3K27 trimethylation in a dominant manner by sequestering an enzymatic subunit of the polycomb repressive complex 2 (PRC2). As a consequence, the epigenetic setting of the cell including DNA methylation is altered and drives gene expression changes towards tumorigenesis (6). |
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| ==Genes and Main Pathways Involved== | | ==Genes and Main Pathways Involved== |
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| + | The lysine 27 to methionine substitution in histone variant H3.3 (H3.3-K27M) is the most common mutation in pediatric high grade gliomas (6). |
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| ==Diagnostic Testing Methods== | | ==Diagnostic Testing Methods== |
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| + | Histopathology, immunohistochemistry, FISH, sequencing, SNP array |
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| ==Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)== | | ==Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)== |
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| + | H3-K27M mutation associated with aggressive behavior and poor prognosis |
| + | Two year survival rate of <10%. |
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| ==Familial Forms== | | ==Familial Forms== |
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| + | MUTYH germline mutation reported in one case (5) |
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| ==Other Information== | | ==Other Information== |
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| + | K27M mutation alters an important site of post-translational modification in the histone H3 variants and leads to altered DNA methylation and gene expression profiles thought to drive gliomagenesis. There are ongoing studies targeting histone modifying enzymes. A small molecule inhibitor of histone demethylase KDM6B (JMJD3) and a histone deacetylase inhibitor panobinostat are under investigation (2,5). |
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| ==Links== | | ==Links== |