[Paper-level Aggregated] PMCID: PMC4654747

Evidence Type(s): Functional

Summary: Mutation: K27M | Summary: The K27M mutation alters the trimethylation status of histone H3, impacting molecular function related to gene regulation in tumor cells. It is linked to alterations in molecular functions, specifically affecting adhesion properties and deregulating genes related to migration and invasion in tumors.

Evidence Type: Functional Mutation: K27I | Summary: The K27I mutation results in a loss of H3K27me3 immunoexpression, indicating an alteration in molecular function. The nucleotide changes 83A>T and 84G>T are part of the K27I mutation and contribute to the alteration in molecular function.

Gene→Variant (gene-first): H3-3B(3021):K27M H3-3B(3021):K27I

Genes: H3-3B(3021)

Variants: K27M K27I

[Paper-level Aggregated] PMCID: PMC4654747

Evidence Type(s): Oncogenic

Summary: Mutation: K27M | Summary: The K27M mutation in H3.3 (H3F3A) is associated with tumor development and progression in diffuse intrinsic pontine glioma (DIPG), driving distinct oncogenic programs. It is detected in biopsy samples and correlates with histological features, indicating its role in tumor development. The mutation is also associated with specific tumor subgroups (H3.1 and H3.3) and contributes to the oncogenic characteristics of the tumors. Additionally, it is used to classify and define specific tumor subtypes, particularly in H3.1 and H3.3 tumors.

Evidence Type: Oncogenic Mutation: K27I | Summary: The K27I mutation in H3.3 (H3F3A) is associated with tumor development in DIPG, contributing to the loss of trimethylation and driving oncogenic behavior. It results in a loss of H3K27me3 immunoexpression, indicating an alteration in molecular function.

Evidence Type: Oncogenic Mutation: H3-G34R/V | Summary: The H3-G34R/V mutations are restricted to cerebral hemispheres, suggesting their role in tumor development or progression.

Evidence Type: Oncogenic Mutation: H3.3-K27I | Summary: The H3.3-K27I mutation is found in pontine tumors, indicating its contribution to tumor development or progression.

Gene→Variant (gene-first): H3-3B(3021):K27M H3-3B(3021):K27I NA:H3-G34R/V NA:H3.3-K27I

Genes: H3-3B(3021) NA

Variants: K27M K27I H3-G34R/V H3.3-K27I

[Paper-level Aggregated] PMCID: PMC4654747

Evidence Type(s): Prognostic

Summary: Mutation: K27M | Summary: Patients with tumors harboring the K27M mutation in H3.3 exhibited significantly earlier relapse and more metastatic recurrences, indicating a poor prognosis. The presence of the K27M mutation correlates with disease outcome, as indicated by clinico-radiological follow-up of DIPG patients showing a significant association with metastatic relapse. Additionally, the K27M mutation is associated with a less aggressive behavior in DIPG, indicating its correlation with disease outcome independent of therapy. Furthermore, the K27M mutation in histone H3.1 is associated with a better overall survival length compared to H3.3-K27M, indicating its prognostic significance in disease outcome.

Gene→Variant (gene-first): H3-3B(3021):K27M

Genes: H3-3B(3021)

Variants: K27M

[Paper-level Aggregated] PMCID: PMC4654747

Evidence Type(s): Diagnostic

Summary: Mutation: K27M | Summary: The K27M mutation is used to classify and define specific tumor subtypes, particularly in H3.1 and H3.3 tumors, and is associated with the proneural-glioblastoma multiforme subtype, indicating its role in disease classification. It can be accurately detected by immunohistochemistry (IHC).

Gene→Variant (gene-first): H3-3B(3021):K27M

Genes: H3-3B(3021)

Variants: K27M

[Paper-level Aggregated] PMCID: PMC4654747

Evidence Type(s): Predictive

Summary: Mutation: K27M | Summary: Patients with the H3.1-K27M mutation show a better clinical response to radiotherapy, suggesting that this mutation may predict treatment response.

Gene→Variant (gene-first): H3-3B(3021):K27M

Genes: H3-3B(3021)

Variants: K27M

[Paragraph-level] PMCID: PMC4654747 Section: RESULTS PassageIndex: 14

Evidence Type(s): Prognostic, Predictive, Oncogenic

Summary: Evidence Type: Prognostic | Mutation: K27M | Summary: The K27M mutation in histone H3.1 is associated with a better overall survival length compared to H3.3-K27M, indicating its prognostic significance in disease outcome. Evidence Type: Predictive | Mutation: K27M | Summary: Patients with the H3.1-K27M mutation show a better clinical response to radiotherapy, suggesting that this mutation may predict treatment response. Evidence Type: Oncogenic | Mutation: K27M | Summary: The K27M mutation in histone H3 is implicated in tumor development and progression, contributing to the oncogenic characteristics of the tumors.

Gene→Variant (gene-first): 3021:K27M

Genes: 3021

Variants: K27M

[Paragraph-level] PMCID: PMC4654747 Section: RESULTS PassageIndex: 13

Evidence Type(s): Prognostic

Summary: Evidence Type: Prognostic | Mutation: K27M | Summary: The K27M mutation is associated with a less aggressive behavior in diffuse intrinsic pontine glioma (DIPG), indicating its correlation with disease outcome independent of therapy.

Gene→Variant (gene-first): 3021:K27M

Genes: 3021

Variants: K27M

[Paragraph-level] PMCID: PMC4654747 Section: RESULTS PassageIndex: 11

Evidence Type(s): Diagnostic, Prognostic, Functional

Summary: Evidence Type: Diagnostic | Mutation: K27M | Summary: The K27M mutation is associated with the proneural-glioblastoma multiforme subtype, indicating its role in classifying and defining this specific disease subtype. Evidence Type: Prognostic | Mutation: K27M | Summary: The presence of the K27M mutation correlates with disease outcome, as indicated by the clinico-radiological follow-up of DIPG patients showing a significant association with metastatic relapse. Evidence Type: Functional | Mutation: K27M | Summary: The K27M mutation is linked to alterations in molecular functions, specifically affecting adhesion properties and deregulating genes related to migration and invasion in tumors.

Gene→Variant (gene-first): 3021:K27M

Genes: 3021

Variants: K27M

[Paragraph-level] PMCID: PMC4654747 Section: RESULTS PassageIndex: 10

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: K27M | Summary: The K27M mutation is associated with driving distinct oncogenic programs, indicating its role in tumor development or progression.

Gene→Variant (gene-first): 3021:K27M

Genes: 3021

Variants: K27M

[Paragraph-level] PMCID: PMC4654747 Section: RESULTS PassageIndex: 9

Evidence Type(s): Oncogenic, Diagnostic

Summary: Evidence Type: Oncogenic | Mutation: K27M | Summary: The K27M mutation is associated with specific tumor subgroups (H3.1 and H3.3) and is implicated in tumor development, particularly in the context of DIPG and pHGG. Evidence Type: Diagnostic | Mutation: K27M | Summary: The K27M mutation is used to classify and define specific tumor subtypes, particularly in H3.1 and H3.3 tumors, indicating its role in disease classification.

Gene→Variant (gene-first): 3021:K27M

Genes: 3021

Variants: K27M

[Paragraph-level] PMCID: PMC4654747 Section: RESULTS PassageIndex: 5

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: H3.3-K27M | Summary: The H3.3-K27M mutation is associated with midline tumors, indicating its contribution to tumor development or progression. Evidence Type: Oncogenic | Mutation: H3-G34R/V | Summary: The H3-G34R/V mutations are restricted to cerebral hemispheres, suggesting their role in tumor development or progression. Evidence Type: Oncogenic | Mutation: H3.3-K27I | Summary: The H3.3-K27I mutation is found in pontine tumors, indicating its contribution to tumor development or progression.

Gene→Variant (gene-first): 3196:G34R/V 3021:K27I 3021:K27M

Genes: 3196 3021

Variants: G34R/V K27I K27M

[Paragraph-level] PMCID: PMC4654747 Section: RESULTS PassageIndex: 4

Evidence Type(s): Diagnostic, Oncogenic, Functional

Summary: Evidence Type: Diagnostic | Mutation: K27M | Summary: The H3-K27M mutation is used to classify and define a subtype of tumors, as it can be accurately detected by immunohistochemistry (IHC). Evidence Type: Oncogenic | Mutation: K27M | Summary: The H3-K27M mutation contributes to tumor development or progression, as indicated by its presence in tumor cells. Evidence Type: Functional | Mutation: K27I | Summary: The K27I mutation results in a loss of H3K27me3 immunoexpression, indicating an alteration in molecular function. Evidence Type: Functional | Mutation: 83A>T | Summary: The nucleotide change 83A>T is part of the K27I mutation and contributes to the alteration in molecular function. Evidence Type: Functional | Mutation: 84G>T | Summary: The nucleotide change 84G>T is part of the K27I mutation and contributes to the alteration in molecular function.

Gene→Variant (gene-first): 7157:83A>T 4613:84G>T 3021:K27I 3021:K27M 126961:lysine-to-isoleucine

Genes: 7157 4613 3021 126961

Variants: 83A>T 84G>T K27I K27M lysine-to-isoleucine

[Paragraph-level] PMCID: PMC4654747 Section: RESULTS PassageIndex: 3

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: K27M | Summary: The H3-K27M mutation is associated with tumor development in DIPG, as indicated by its detection in biopsy samples and correlation with histological features. Evidence Type: Functional | Mutation: K27M | Summary: The K27M mutation alters the trimethylation status of histone H3, impacting molecular function related to gene regulation in tumor cells.

Gene→Variant (gene-first): 3021:K27M 3021:lysine 27

Genes: 3021

Variants: K27M lysine 27

[Paragraph-level] PMCID: PMC4654747 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Oncogenic, Prognostic

Summary: Evidence Type: Oncogenic | Mutation: K27M | Summary: The K27M mutation in H3.3 (H3F3A) contributes to tumor development and progression in diffuse intrinsic pontine glioma (DIPG), driving distinct oncogenic programs. Evidence Type: Oncogenic | Mutation: K27I | Summary: The K27I mutation in H3F3A is associated with tumor development in DIPG, contributing to the loss of trimethylation and driving oncogenic behavior. Evidence Type: Prognostic | Mutation: K27M | Summary: Patients with tumors harboring the K27M mutation in H3.3 exhibited significantly earlier relapse and more metastatic recurrences, indicating a poor prognosis.

Gene→Variant (gene-first): 3021:K27I 3021:K27M 126961:lysine-to-isoleucine

Genes: 3021 126961

Variants: K27I K27M lysine-to-isoleucine

[Paper-level Aggregated] PMCID: PMC4654747

Evidence Type(s): Oncogenic, Prognostic, Functional

Justification: Oncogenic: The study indicates that mutations in histone H3, specifically K27M and K27I, drive distinct oncogenic programs in DIPG, with H3.3-K27M mutations leading to a proneural/oligodendroglial phenotype and a pro-metastatic gene expression signature. Prognostic: The findings demonstrate that patients with H3.1-K27M mutations have a better overall survival and clinical response to radiotherapy compared to those with H3.3-K27M mutations, indicating that the type of histone mutation is a significant prognostic factor. Functional: The study assesses the functional impact of histone mutations on gene expression profiles and tumor behavior, showing that specific mutations lead to alterations in trimethylation and gene expression that influence tumor characteristics and patient outcomes.

Gene→Variant (gene-first): TP53(7157):83A>T MYCN(4613):84G>T H3-3B(3021):K27I H3-3B(3021):K27M H3C14(126961):lysine-to-isoleucine TLX2(3196):G34R/V H3-3B(3021):lysine 27

Genes: TP53(7157) MYCN(4613) H3-3B(3021) H3C14(126961) TLX2(3196)

Variants: 83A>T 84G>T K27I K27M lysine-to-isoleucine G34R/V lysine 27

[Paragraph-level] PMCID: PMC4654747 Section: RESULTS PassageIndex: 14

Evidence Type(s): Diagnostic, Prognostic, Oncogenic

Justification: Diagnostic: The passage discusses the association of H3.1-K27M tumors with clinical characteristics and outcomes, indicating its role in defining and classifying the disease. Prognostic: The variant K27M is correlated with overall survival outcomes, with H3.1 mutations showing a better prognosis compared to H3.3 mutations, independent of therapy. Oncogenic: The mention of H3.1-K27M tumors suggests that this somatic variant contributes to tumor development or progression, as it is associated with clinical characteristics and outcomes in cancer patients.

Gene→Variant (gene-first): 3021:K27M

Genes: 3021

Variants: K27M

[Paragraph-level] PMCID: PMC4654747 Section: RESULTS PassageIndex: 13

Evidence Type(s): Prognostic, Diagnostic

Justification: Prognostic: The K27M mutation is associated with disease behavior, indicating a correlation with disease outcome, specifically suggesting a less aggressive behavior in DIPG. Diagnostic: The mention of the K27M mutation being associated with DIPG suggests its role in defining or classifying this specific disease subtype.

Gene→Variant (gene-first): 3021:K27M

Genes: 3021

Variants: K27M

[Paragraph-level] PMCID: PMC4654747 Section: RESULTS PassageIndex: 11

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the strong enrichment of the K27M variant in specific tumor subtypes, indicating its association with the proneural-glioblastoma multiforme (GBM) and oligodendrocytic or neural signatures, which helps classify the disease. Oncogenic: The K27M variant is implicated in tumor development, as evidenced by its association with oligodendroglial differentiation and the observation of metastatic relapse in patients with H3F3A mutations, suggesting a role in tumor progression.

Gene→Variant (gene-first): 3021:K27M

Genes: 3021

Variants: K27M

[Paragraph-level] PMCID: PMC4654747 Section: RESULTS PassageIndex: 10

Evidence Type(s): Oncogenic

Justification: Oncogenic: The passage indicates that K27M mutations in H3.3 and H3.1 contribute to distinct oncogenic programs, suggesting their role in tumor development or progression.

Gene→Variant (gene-first): 3021:K27M

Genes: 3021

Variants: K27M

[Paragraph-level] PMCID: PMC4654747 Section: RESULTS PassageIndex: 9

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the exclusive presence of the K27M variant in specific tumor subgroups (H3.1-K27M and H3.3-K27M), indicating its role in classifying these tumors. Oncogenic: The K27M variant is associated with specific tumor subgroups and is implicated in tumor development, as indicated by its exclusive presence in H3.1 and H3.3 tumors.

Gene→Variant (gene-first): 3021:K27M

Genes: 3021

Variants: K27M

[Paragraph-level] PMCID: PMC4654747 Section: RESULTS PassageIndex: 5

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the identification of specific mutations (H3.3-K27M, H3-G34R/V, H3.1- and H3.2-K27M, H3.3 K27I) in different tumor locations, indicating their association with specific tumor types, which supports their use in defining or classifying disease subtypes. Oncogenic: The mention of mutations being identified in specific tumor types suggests that these variants contribute to tumor development or progression, indicating their oncogenic potential.

Gene→Variant (gene-first): 3196:G34R/V 3021:K27I 3021:K27M

Genes: 3196 3021

Variants: G34R/V K27I K27M

[Paragraph-level] PMCID: PMC4654747 Section: RESULTS PassageIndex: 4

Evidence Type(s): Diagnostic, Functional

Justification: Diagnostic: The passage discusses the detection of H3-K27M mutations and their association with immunohistochemistry (IHC) staining, indicating the use of these variants to classify or define a subtype of disease. Functional: The passage mentions the loss of H3K27me3 immunoexpression associated with the K27I variant, indicating an alteration in molecular function related to protein activity or modification.

Gene→Variant (gene-first): 7157:83A>T 4613:84G>T 3021:K27I 3021:K27M 126961:lysine-to-isoleucine

Genes: 7157 4613 3021 126961

Variants: 83A>T 84G>T K27I K27M lysine-to-isoleucine

[Paragraph-level] PMCID: PMC4654747 Section: RESULTS PassageIndex: 3

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the correlation of the H3-K27M mutation with the classification of DIPG samples, indicating its role in defining or confirming the disease subtype. Oncogenic: The mention of the H3-K27M mutation in the context of tumor samples suggests that it contributes to tumor development or progression, characteristic of oncogenic variants.

Gene→Variant (gene-first): 3021:K27M 3021:lysine 27

Genes: 3021

Variants: K27M lysine 27

[Paragraph-level] PMCID: PMC4654747 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Oncogenic, Predictive

Justification: Oncogenic: The passage discusses how mutations in histone H3, specifically K27M and K27I, contribute to tumor development and progression in diffuse intrinsic pontine glioma (DIPG), indicating their role as somatic variants driving distinct oncogenic programs. Predictive: The K27M mutation is associated with a lack of clinical response to radiotherapy and earlier relapse, suggesting that this variant correlates with treatment resistance and impacts patient outcomes.

Gene→Variant (gene-first): 3021:K27I 3021:K27M 126961:lysine-to-isoleucine

Genes: 3021 126961

Variants: K27I K27M lysine-to-isoleucine