[Paper-level Aggregated] PMCID: PMC4159563

Evidence Type(s): Functional

Summary: Mutation: p.Glu545Gly | Summary: The p.Glu545Gly alteration in PIK3CA is a mutation that may alter the molecular function of the protein, contributing to tumorigenesis.

Evidence Type: Functional Mutation: p.Gly328Val | Summary: The p.Gly328Val substitution in ACVR1 is a mutation that may affect the molecular function of the protein, potentially playing a role in tumor development.

Gene→Variant (gene-first): PIK3CA(5290):p.Glu545Gly ACVR1(90):p.Gly328Val

Genes: PIK3CA(5290) ACVR1(90)

Variants: p.Glu545Gly p.Gly328Val

[Paper-level Aggregated] PMCID: PMC4159563

Evidence Type(s): Oncogenic

Summary: Mutation: K27M | Summary: The K27M mutation in histone H3 is associated with high-grade astrocytomas and contributes to tumor development and progression in diffuse intrinsic pontine glioma (DIPG). It is linked to leptomeningeal dissemination and is considered an oncogenic variant due to its role in tumor development.

Gene→Variant (gene-first): ACVR1(90):K27M

Genes: ACVR1(90)

Variants: K27M

[Paper-level Aggregated] PMCID: PMC4159563

Evidence Type(s): Prognostic

Summary: Mutation: K27M | Summary: The K27M-H3 mutation correlates with disease behavior and outcomes in pediatric brainstem gliomas, indicating it may not predict outcomes accurately according to the current WHO grading scheme. It is associated with worse overall survival in patients with leptomeningeal spread, averaging 0.63 years compared to 1.84 years for wild-type cases. Additionally, the K27M mutation in histone H3 is linked to worse overall survival in DIPG patients compared to those without histone mutations, highlighting its prognostic significance.

Gene→Variant (gene-first): ACVR1(90):K27M

Genes: ACVR1(90)

Variants: K27M

[Paper-level Aggregated] PMCID: PMC4159563

Evidence Type(s): Diagnostic

Summary: Mutation: K27M | Summary: The presence of the K27M-H3 mutation is used to classify and define the histological subtype of astrocytomas in DIPG cases. It is associated with specific histological features that can help in tumor classification, serving as a diagnostic marker for tumors in DIPG patients.

Gene→Variant (gene-first): ACVR1(90):K27M

Genes: ACVR1(90)

Variants: K27M

[Paragraph-level] PMCID: PMC4159563 Section: RESULTS PassageIndex: 9

Evidence Type(s): Prognostic, Diagnostic, Oncogenic

Summary: Evidence Type: Prognostic | Mutation: K27M | Summary: The K27M mutation in histone H3 is associated with worse overall survival in DIPG patients compared to those without histone mutations, indicating its prognostic significance. Evidence Type: Diagnostic | Mutation: K27M | Summary: The presence of the K27M mutation in histone H3 is used to classify and define the subtype of tumors in DIPG patients, serving as a diagnostic marker. Evidence Type: Oncogenic | Mutation: K27M | Summary: The K27M mutation in histone H3 contributes to tumor development and progression in DIPG, indicating its oncogenic potential.

Gene→Variant (gene-first): 90:K27M

Genes: 90

Variants: K27M

[Paragraph-level] PMCID: PMC4159563 Section: RESULTS PassageIndex: 8

Evidence Type(s): Diagnostic, Oncogenic

Summary: Evidence Type: Diagnostic | Mutation: K27M | Summary: The K27M mutation is associated with specific histological features, which can be used to classify or define certain types of tumors. Evidence Type: Oncogenic | Mutation: K27M | Summary: The K27M mutation contributes to tumor development and progression, indicating its role as an oncogenic variant.

Gene→Variant (gene-first): 90:K27M

Genes: 90

Variants: K27M

[Paragraph-level] PMCID: PMC4159563 Section: RESULTS PassageIndex: 7

Evidence Type(s): Prognostic, Oncogenic, Functional

Summary: Evidence Type: Prognostic | Mutation: K27M | Summary: The K27M mutation is associated with worse overall survival in patients with leptomeningeal spread, averaging 0.63 years compared to 1.84 years for wild-type cases. Evidence Type: Oncogenic | Mutation: K27M | Summary: The K27M mutation contributes to tumor development, as indicated by its presence in cases of GBM and its association with leptomeningeal dissemination. Evidence Type: Functional | Mutation: p.Glu545Gly | Summary: The p.Glu545Gly alteration in PIK3CA is a mutation that may alter the molecular function of the protein, contributing to tumorigenesis. Evidence Type: Functional | Mutation: p.Gly328Val | Summary: The p.Gly328Val substitution in ACVR1 is a mutation that may affect the molecular function of the protein, potentially playing a role in tumor development.

Gene→Variant (gene-first): 90:K27M 5290:p.Glu545Gly 90:p.Gly328Val

Genes: 90 5290

Variants: K27M p.Glu545Gly p.Gly328Val

[Paragraph-level] PMCID: PMC4159563 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Oncogenic, Diagnostic, Prognostic

Summary: Evidence Type: Oncogenic | Mutation: K27M | Summary: The K27M-H3 mutation is associated with high-grade astrocytomas and contributes to tumor development in diffuse intrinsic pontine glioma (DIPG). Evidence Type: Diagnostic | Mutation: K27M | Summary: The presence of the K27M-H3 mutation is used to classify and define the histological subtype of astrocytomas in DIPG cases. Evidence Type: Prognostic | Mutation: K27M | Summary: The K27M-H3 mutation correlates with disease behavior and outcome in pediatric brainstem gliomas, indicating that it may not predict outcomes accurately according to the current WHO grading scheme.

Gene→Variant (gene-first): 90:K27M

Genes: 90

Variants: K27M

[Paper-level Aggregated] PMCID: PMC4159563

Evidence Type(s): Prognostic, Oncogenic, Predictive

Justification: Prognostic: The presence of the K27M mutation in histone H3 is associated with worse overall survival in DIPG patients, as indicated by the significant difference in survival rates between patients with K27M mutations and those without. Oncogenic: The K27M-H3 mutation is found exclusively in high-grade astrocytomas and is associated with aggressive clinical behavior, suggesting its role in tumorigenesis. Predictive: The study indicates that histone mutation status, particularly K27M, is a significant predictor of overall survival, which may inform treatment decisions for DIPG patients.

Gene→Variant (gene-first): ACVR1(90):K27M PIK3CA(5290):p.Glu545Gly ACVR1(90):p.Gly328Val

Genes: ACVR1(90) PIK3CA(5290)

Variants: K27M p.Glu545Gly p.Gly328Val

[Paragraph-level] PMCID: PMC4159563 Section: RESULTS PassageIndex: 9

Evidence Type(s): Prognostic, Diagnostic, Oncogenic

Justification: Prognostic: The passage indicates that patients with the K27M mutation in histone H3 have worse overall survival compared to patients with no histone mutations, suggesting a correlation between the variant and disease outcome. Diagnostic: The K27M mutation is associated with specific tumor histologies and is used to classify patients into different groups based on their histone mutation status, indicating its role in defining disease subtypes. Oncogenic: The K27M mutation in histone H3 is described as contributing to tumor development, as it is found in a significant proportion of tumors and correlates with specific tumor characteristics.

Gene→Variant (gene-first): 90:K27M

Genes: 90

Variants: K27M

[Paragraph-level] PMCID: PMC4159563 Section: RESULTS PassageIndex: 8

Evidence Type(s): None

Justification: Not enough information in this passage.

Gene→Variant (gene-first): 90:K27M

Genes: 90

Variants: K27M

[Paragraph-level] PMCID: PMC4159563 Section: RESULTS PassageIndex: 7

Evidence Type(s): Prognostic, Oncogenic

Justification: Prognostic: The passage discusses overall survival rates for patients with and without leptomeningeal spread, indicating that the presence of the K27M mutation correlates with worse survival outcomes. Oncogenic: The K27M variant is mentioned in the context of tumor spread and is associated with specific tumor types (GBM), suggesting its role in tumor development or progression.

Gene→Variant (gene-first): 90:K27M 5290:p.Glu545Gly 90:p.Gly328Val

Genes: 90 5290

Variants: K27M p.Glu545Gly p.Gly328Val

[Paragraph-level] PMCID: PMC4159563 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The K27M-H3 mutation is described as being exclusively found in tumors with specific WHO grade II-IV astrocytoma histology, indicating its role in classifying and defining the disease subtype. Oncogenic: The passage indicates that the K27M-H3 mutation is associated with tumors that behave clinically as high-grade astrocytomas, suggesting its contribution to tumor development or progression.

Gene→Variant (gene-first): 90:K27M

Genes: 90

Variants: K27M

[Paragraph-level] PMCID: PMC4159563 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The K27M-H3 mutation is described as being exclusively found in tumors with specific WHO grade II-IV astrocytoma histology, indicating its role in classifying and defining the disease subtype. Oncogenic: The passage indicates that the K27M-H3 mutation is associated with tumors that behave clinically as high-grade astrocytomas, suggesting its contribution to tumor development or progression.

Gene→Variant (gene-first): 90:K27M

Genes: 90

Variants: K27M