K27M mutation in histone H3.3 defines clinically and biologically distinct subgroups of pediatric diffuse intrinsic pontine gliomas
[Paper-level Aggregated] PMCID: PMC3422615
Evidence Type(s): Functional
Summary: Mutation: K27M | Summary: The K27M mutation alters molecular characteristics in H3.3, impacting the biochemical function relevant to tumor biology.
Gene→Variant (gene-first): H3-3B(3021):K27M
Genes: H3-3B(3021)
Variants: K27M
K27M mutation in histone H3.3 defines clinically and biologically distinct subgroups of pediatric diffuse intrinsic pontine gliomas
[Paper-level Aggregated] PMCID: PMC3422615
Evidence Type(s): Oncogenic
Summary: Mutation: K27M | Summary: The K27M-H3.3 mutation is prevalent in pediatric glioblastomas and is recurrently identified in DIPG samples, contributing to tumor development and progression. It is associated with specific chromosomal alterations and significant focal copy number alterations, indicating its role in tumor biology. The mutation is found in DIPG samples that also harbor ATRX mutations, suggesting its involvement in tumor progression. Additionally, the K27M mutation correlates with poor survival outcomes in affected patients, highlighting its oncogenic significance.
Evidence Type: Oncogenic Mutation: G34V/R | Summary: The G34V/R mutation is associated with GBM samples that also carry ATRX and TP53 mutations, indicating its contribution to tumor development.
Gene→Variant (gene-first): H3-3B(3021):K27M H3-3B(3021):G34V/R
Genes: H3-3B(3021)
Variants: K27M G34V/R
K27M mutation in histone H3.3 defines clinically and biologically distinct subgroups of pediatric diffuse intrinsic pontine gliomas
[Paper-level Aggregated] PMCID: PMC3422615
Evidence Type(s): Prognostic
Summary: Mutation: K27M | Summary: The K27M-H3.3 mutation is universally associated with short survival in DIPG and correlates with significantly worse overall survival in DIPG patients compared to wild-type tumors, indicating its prognostic significance in disease outcome.
Gene→Variant (gene-first): H3-3B(3021):K27M
Genes: H3-3B(3021)
Variants: K27M
K27M mutation in histone H3.3 defines clinically and biologically distinct subgroups of pediatric diffuse intrinsic pontine gliomas
[Paper-level Aggregated] PMCID: PMC3422615
Evidence Type(s): Diagnostic
Summary: Mutation: K27M | Summary: The K27M-H3.3 mutation is used to define clinically and biologically distinct subgroups in pediatric glioblastomas, supporting its role in diagnostic testing.
Gene→Variant (gene-first): H3-3B(3021):K27M
Genes: H3-3B(3021)
Variants: K27M
H3.3 mutational status and survival data were available for 39 DIPG patients, 27 of whom (69 %) carried the K27M-H3.3 mutation. The mean overall survival for patients with K27M-H3.3 mutated tumors was 0.73 years (+-0.48)
[Paragraph-level] PMCID: PMC3422615 Section: RESULTS PassageIndex: 12
Evidence Type(s): Prognostic, Oncogenic
Summary: Evidence Type: Prognostic | Mutation: K27M | Summary: The K27M-H3.3 mutation correlates with significantly worse overall survival in DIPG patients compared to wild-type tumors, indicating its role as a prognostic factor for disease outcome. Evidence Type: Oncogenic | Mutation: K27M | Summary: The K27M-H3.3 mutation contributes to tumor development or progression in DIPG, as evidenced by its association with poor survival outcomes in affected patients.
Gene→Variant (gene-first): 3021:K27M
Genes: 3021
Variants: K27M
Focal recurrent gains and deletion in both groups were further analyzed using GISTIC2.0. H3.3 wild-type patients had significant focal gains/amplifications of regions 2p25.1 (q = 0.028) and 2p24.3 (q = 0.028) including t
[Paragraph-level] PMCID: PMC3422615 Section: RESULTS PassageIndex: 10
Evidence Type(s): Oncogenic
Summary: Evidence Type: Oncogenic | Mutation: K27M | Summary: The K27M mutation is associated with significant focal copy number alterations and is implicated in tumor development, particularly in the context of H3.3 mutant groups.
Gene→Variant (gene-first): 3021:K27M
Genes: 3021
Variants: K27M
Analysis of DNA copy number alterations in K27M-H3.3 versus H3.3 wild-type DIPG samples showed not only the areas of overlap but also major differences between both groups. Large chromosomal copy number alterations commo
[Paragraph-level] PMCID: PMC3422615 Section: RESULTS PassageIndex: 9
Evidence Type(s): Oncogenic, Functional
Summary: Evidence Type: Oncogenic | Mutation: K27M | Summary: The K27M-H3.3 mutation is associated with specific chromosomal alterations that contribute to tumor development in DIPG samples. Evidence Type: Functional | Mutation: K27M | Summary: The K27M mutation alters molecular characteristics in H3.3, impacting the biochemical function relevant to tumor biology.
Gene→Variant (gene-first): 3021:K27M
Genes: 3021
Variants: K27M
As previously described, a significant number of DIPG samples carried mutations in TP53, (17/22, 77 %). Fourteen of these samples carrying TP53 mutations were also mutant for K27M-H3.3 (Table 1). However, even though the
[Paragraph-level] PMCID: PMC3422615 Section: RESULTS PassageIndex: 7
Evidence Type(s): Oncogenic
Summary: Evidence Type: Oncogenic | Mutation: K27M | Summary: The K27M mutation in H3.3 is associated with DIPG samples and contributes to tumor development or progression, as indicated by its presence in a significant number of cases.
Gene→Variant (gene-first): 3021:K27M
Genes: 3021
Variants: K27M
We previously showed that G34V/R-H3.3 GBM samples universally also carried ATRX and TP53 mutations (13/13), while K27M-H3.3 GBM samples had significant, albeit lower, overlap with ATRX and TP53 mutations (respectively, 3
[Paragraph-level] PMCID: PMC3422615 Section: RESULTS PassageIndex: 5
Evidence Type(s): Oncogenic
Summary: Evidence Type: Oncogenic | Mutation: G34V/R | Summary: The G34V/R mutation is associated with GBM samples that also carry ATRX and TP53 mutations, indicating its contribution to tumor development. Evidence Type: Oncogenic | Mutation: K27M | Summary: The K27M mutation is found in DIPG samples that also harbor ATRX mutations, suggesting its role in tumor progression.
Gene→Variant (gene-first): 3021:G34V/R 3021:K27M
Genes: 3021
Variants: G34V/R K27M
We sequenced H3F3A in 42 DIPG samples comprising either biopsy material prior to any treatment (n = 16) or autopsy samples (n = 26, one sample from untreated patient at autopsy; DIPG02). We identified the recurrent mutat
[Paragraph-level] PMCID: PMC3422615 Section: RESULTS PassageIndex: 3
Evidence Type(s): Oncogenic
Summary: Evidence Type: Oncogenic | Mutation: K27M | Summary: The K27M mutation in Histone H3.3 is recurrently identified in DIPG samples, indicating its contribution to tumor development and progression.
Gene→Variant (gene-first): 3021:G34V/R 3021:K27M
Genes: 3021
Variants: G34V/R K27M
Pediatric glioblastomas (GBM) including diffuse intrinsic pontine gliomas (DIPG) are devastating brain tumors with no effective therapy. Here, we investigated clinical and biological impacts of histone H3.3 mutations. Fo
[Paragraph-level] PMCID: PMC3422615 Section: ABSTRACT PassageIndex: 1
Evidence Type(s): Oncogenic, Prognostic, Diagnostic
Summary: Evidence Type: Oncogenic | Mutation: K27M | Summary: The K27M-H3.3 mutation is prevalent in pediatric glioblastomas and contributes to tumor development, defining clinically and biologically distinct subgroups. Evidence Type: Prognostic | Mutation: K27M | Summary: The K27M-H3.3 mutation is universally associated with short survival in DIPG, indicating its prognostic significance in disease outcome. Evidence Type: Diagnostic | Mutation: K27M | Summary: The K27M-H3.3 mutation is used to define clinically and biologically distinct subgroups in pediatric glioblastomas, supporting its role in diagnostic testing.
Gene→Variant (gene-first): 3021:G34V 3021:G34V/R 3021:K27M
Genes: 3021
Variants: G34V G34V/R K27M
K27M mutation in histone H3.3 defines clinically and biologically distinct subgroups of pediatric diffuse intrinsic pontine gliomas
[Paper-level Aggregated] PMCID: PMC3422615
Evidence Type(s): Prognostic, Oncogenic, Predictive
Justification: Prognostic: The K27M-H3.3 mutation is associated with significantly worse overall survival in DIPG patients, with a mean survival of 0.73 years compared to 4.59 years for wild-type patients, indicating its role as a prognostic marker. Oncogenic: The K27M-H3.3 mutation is prevalent in DIPGs and is associated with specific copy number alterations and distinct clinical outcomes, suggesting its role in tumorigenesis. Predictive: The findings advocate for H3.3-mutation testing at diagnosis to inform therapeutic trial design and clinical decision-making, indicating its potential to predict treatment response.
Gene→Variant (gene-first): H3-3B(3021):G34V/R H3-3B(3021):K27M H3-3B(3021):G34V
Genes: H3-3B(3021)
Variants: G34V/R K27M G34V
H3.3 mutational status and survival data were available for 39 DIPG patients, 27 of whom (69 %) carried the K27M-H3.3 mutation. The mean overall survival for patients with K27M-H3.3 mutated tumors was 0.73 years (+-0.48)
[Paragraph-level] PMCID: PMC3422615 Section: RESULTS PassageIndex: 12
Evidence Type(s): Prognostic, Diagnostic
Justification: Prognostic: The passage discusses the correlation between the K27M-H3.3 mutation and overall survival in DIPG patients, indicating that patients with this mutation have significantly worse survival outcomes compared to those with wild-type tumors. Diagnostic: The K27M-H3.3 mutation is associated with the classification of DIPG patients, as it is mentioned that 69% of the patients carried this mutation, which is relevant for defining their disease status.
Gene→Variant (gene-first): 3021:K27M
Genes: 3021
Variants: K27M
Focal recurrent gains and deletion in both groups were further analyzed using GISTIC2.0. H3.3 wild-type patients had significant focal gains/amplifications of regions 2p25.1 (q = 0.028) and 2p24.3 (q = 0.028) including t
[Paragraph-level] PMCID: PMC3422615 Section: RESULTS PassageIndex: 10
Evidence Type(s): Oncogenic, Diagnostic
Justification: Oncogenic: The passage discusses frequent focal copy number alterations in the K27M-H3.3 group, indicating that the K27M variant is associated with tumor development through specific genetic alterations. Diagnostic: The mention of the K27M-H3.3 group suggests that the K27M variant is used to classify or define a specific subtype of tumors, indicating its role in disease classification.
Gene→Variant (gene-first): 3021:K27M
Genes: 3021
Variants: K27M
Analysis of DNA copy number alterations in K27M-H3.3 versus H3.3 wild-type DIPG samples showed not only the areas of overlap but also major differences between both groups. Large chromosomal copy number alterations commo
[Paragraph-level] PMCID: PMC3422615 Section: RESULTS PassageIndex: 9
Evidence Type(s): Oncogenic
Justification: Oncogenic: The passage discusses the K27M-H3.3 mutation in the context of DNA copy number alterations in tumors, indicating its role in tumor development or progression through the identification of specific chromosomal changes associated with this variant.
Gene→Variant (gene-first): 3021:K27M
Genes: 3021
Variants: K27M
As previously described, a significant number of DIPG samples carried mutations in TP53, (17/22, 77 %). Fourteen of these samples carrying TP53 mutations were also mutant for K27M-H3.3 (Table 1). However, even though the
[Paragraph-level] PMCID: PMC3422615 Section: RESULTS PassageIndex: 7
Evidence Type(s): Diagnostic, Oncogenic
Justification: Diagnostic: The passage discusses the presence of the K27M variant in DIPG samples and its association with TP53 mutations, indicating its role in classifying or defining a subtype of disease. Oncogenic: The K27M variant is mentioned in the context of mutations found in DIPG samples, suggesting its contribution to tumor development or progression in this specific cancer type.
Gene→Variant (gene-first): 3021:K27M
Genes: 3021
Variants: K27M
We previously showed that G34V/R-H3.3 GBM samples universally also carried ATRX and TP53 mutations (13/13), while K27M-H3.3 GBM samples had significant, albeit lower, overlap with ATRX and TP53 mutations (respectively, 3
[Paragraph-level] PMCID: PMC3422615 Section: RESULTS PassageIndex: 5
Evidence Type(s): Diagnostic, Oncogenic
Justification: Diagnostic: The passage discusses the association of the K27M-H3.3 mutation with ATRX mutations in DIPG samples, indicating its role in defining or classifying a subtype of disease. Oncogenic: The K27M-H3.3 mutation is mentioned in the context of its presence in GBM samples, suggesting its contribution to tumor development or progression.
Gene→Variant (gene-first): 3021:G34V/R 3021:K27M
Genes: 3021
Variants: G34V/R K27M
We sequenced H3F3A in 42 DIPG samples comprising either biopsy material prior to any treatment (n = 16) or autopsy samples (n = 26, one sample from untreated patient at autopsy; DIPG02). We identified the recurrent mutat
[Paragraph-level] PMCID: PMC3422615 Section: RESULTS PassageIndex: 3
Evidence Type(s): Diagnostic, Oncogenic
Justification: Diagnostic: The K27M mutation is identified as being present at diagnosis in DIPG samples, indicating its role in defining the disease subtype. Oncogenic: The K27M mutation contributes to tumor development in DIPG, as it is recurrently found in the samples analyzed, suggesting its role in tumor progression.
Gene→Variant (gene-first): 3021:G34V/R 3021:K27M
Genes: 3021
Variants: G34V/R K27M
Pediatric glioblastomas (GBM) including diffuse intrinsic pontine gliomas (DIPG) are devastating brain tumors with no effective therapy. Here, we investigated clinical and biological impacts of histone H3.3 mutations. Fo
[Paragraph-level] PMCID: PMC3422615 Section: ABSTRACT PassageIndex: 1
Evidence Type(s): Diagnostic, Prognostic, Oncogenic
Justification: Diagnostic: K27M-H3.3 mutation defines clinically and biologically distinct subgroups in DIPG, indicating its use in classifying the disease. Prognostic: K27M-H3.3 is universally associated with short survival in DIPG, while patients wild-type for H3.3 show improved survival, indicating its correlation with disease outcome. Oncogenic: The K27M-H3.3 mutation contributes to tumor development or progression in pediatric glioblastomas, as indicated by its prevalence in DIPG and association with specific copy number changes.
Gene→Variant (gene-first): 3021:G34V 3021:G34V/R 3021:K27M
Genes: 3021
Variants: G34V G34V/R K27M
Pediatric glioblastomas (GBM) including diffuse intrinsic pontine gliomas (DIPG) are devastating brain tumors with no effective therapy. Here, we investigated clinical and biological impacts of histone H3.3 mutations. Fo
[Paragraph-level] PMCID: PMC3422615 Section: ABSTRACT PassageIndex: 1
Evidence Type(s): Diagnostic, Prognostic, Oncogenic
Justification: Diagnostic: K27M-H3.3 mutation defines clinically and biologically distinct subgroups in DIPG, indicating its use in classifying the disease. Prognostic: K27M-H3.3 is universally associated with short survival in DIPG, while patients wild-type for H3.3 show improved survival, indicating its correlation with disease outcome. Oncogenic: The K27M-H3.3 mutation contributes to tumor development or progression in pediatric glioblastomas, as indicated by its prevalence in DIPG and association with specific copy number changes.
Gene→Variant (gene-first): 3021:G34V 3021:G34V/R 3021:K27M
Genes: 3021
Variants: G34V G34V/R K27M