[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

[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

[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

[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

[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

[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

[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

[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

[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