[Paper-level Aggregated] PMCID: PMC7294133

Evidence Type(s): Functional

Summary: Mutation: V871I | Summary: The EPHB4-V871I variant does not impair EPHB4 expression at the mRNA and protein levels, but alters molecular function related to cellular proliferation and migration in neuroblastoma (NB) cell lines. It is associated with increased propagation rates, enhanced migration properties in wound-healing experiments, and a higher number of colonies formed in soft agar assays compared to wild type and empty vector controls. Additionally, the variant increases the expression of downstream target genes and enhances phosphorylation of the ERK1-2 pathway, indicating a significant alteration in molecular or biochemical processes.

Gene→Variant (gene-first): EPHB4(2050):V871I

Genes: EPHB4(2050)

Variants: V871I

[Paper-level Aggregated] PMCID: PMC7294133

Evidence Type(s): Oncogenic

Summary: Mutation: F1174L | Summary: The F1174L mutation in the ALK gene is identified as a somatic variant that is frequently observed in neuroblastoma, suggesting its contribution to tumor development or progression.

Evidence Type: Oncogenic Mutation: V871I | Summary: The V871I variant in the EPHB4 gene contributes to tumor development and progression in neuroblastoma by increasing proliferation, migration, and invasion properties in cancer cell lines. It is associated with a high pathogenic score and impacts downstream signaling pathways and gene expression, indicating its role in tumor development or progression.

Gene→Variant (gene-first): ALK(238):F1174L EPHB4(2050):V871I

Genes: ALK(238) EPHB4(2050)

Variants: F1174L V871I

[Paper-level Aggregated] PMCID: PMC7294133

Evidence Type(s): Prognostic

Summary: Mutation: V871I | Summary: Higher expression of EPHB4, associated with the V871I variant, correlates with advanced disease stages and poor overall survival in neuroblastoma patients.

Gene→Variant (gene-first): EPHB4(2050):V871I

Genes: EPHB4(2050)

Variants: V871I

[Paper-level Aggregated] PMCID: PMC7294133

Evidence Type(s): Diagnostic

Summary: Mutation: V871I | Summary: The EPHB4-V871I mutation is identified in neuroblastoma (NB) patients, suggesting its role in defining or classifying the disease.

Gene→Variant (gene-first): EPHB4(2050):V871I

Genes: EPHB4(2050)

Variants: V871I

[Paper-level Aggregated] PMCID: PMC7294133

Evidence Type(s): Predictive

Summary: Mutation: V871I | Summary: The variant EPHB4-V871I is associated with a response to treatment with TK inhibitors, indicating its predictive value in therapy sensitivity. Additionally, the use of EPHB4 inhibitors, which target the effects of the V871I variant, suggests potential therapeutic strategies for neuroblastoma patients.

Gene→Variant (gene-first): EPHB4(2050):V871I

Genes: EPHB4(2050)

Variants: V871I

[Paragraph-level] PMCID: PMC7294133 Section: ABSTRACT PassageIndex: 2

Evidence Type(s): Oncogenic, Functional, Prognostic, Predictive

Summary: Evidence Type: Oncogenic | Mutation: V871I | Summary: The V871I variant in the EPHB4 gene contributes to tumor development and progression in neuroblastoma by increasing proliferation, migration, and invasion properties in cancer cell lines. Evidence Type: Functional | Mutation: V871I | Summary: The V871I variant alters molecular function by affecting the phosphorylation of the ERK1-2 pathway and influencing the expression of target genes related to cancer progression. Evidence Type: Prognostic | Mutation: V871I | Summary: Higher expression of EPHB4, associated with the V871I variant, correlates with advanced disease stages and poor overall survival in neuroblastoma patients. Evidence Type: Predictive | Mutation: V871I | Summary: The use of EPHB4 inhibitors, which target the effects of the V871I variant, suggests potential therapeutic strategies for neuroblastoma patients.

Gene→Variant (gene-first): 2050:V871I

Genes: 2050

Variants: V871I

[Paragraph-level] PMCID: PMC7294133 Section: RESULTS PassageIndex: 16

Evidence Type(s): Predictive, Functional

Summary: Evidence Type: Predictive | Mutation: V871I | Summary: The variant EPHB4-V871I is associated with a response to treatment with TK inhibitors, indicating its predictive value in therapy sensitivity. Evidence Type: Functional | Mutation: V871I | Summary: The variant EPHB4-V871I alters the phenotype in neuroblastoma (NB) cell lines, suggesting a functional impact on molecular or biochemical processes.

Gene→Variant (gene-first): 2050:V871I

Genes: 2050

Variants: V871I

[Paragraph-level] PMCID: PMC7294133 Section: RESULTS PassageIndex: 15

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: V871I | Summary: The EPHB4-V871I variant is associated with increased expression levels of downstream target genes and enhanced phosphorylation of the ERK1-2 pathway, indicating an alteration in molecular function. Evidence Type: Oncogenic | Mutation: V871I | Summary: The EPHB4-V871I variant contributes to tumor development or progression as suggested by its impact on downstream signaling pathways and gene expression.

Gene→Variant (gene-first): 2050:V871I

Genes: 2050

Variants: V871I

[Paragraph-level] PMCID: PMC7294133 Section: RESULTS PassageIndex: 14

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: V871I | Summary: The EPHB4-V871I variant alters molecular function by increasing the expression of target genes and enhancing the phosphorylation of the ERK1-2 pathway.

Gene→Variant (gene-first): 2050:V871I

Genes: 2050

Variants: V871I

[Paragraph-level] PMCID: PMC7294133 Section: RESULTS PassageIndex: 13

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: V871I | Summary: The V871I mutation in EPHB4 alters molecular function, as indicated by the increased number of colonies formed in the colony formation assay in soft agar compared to wild type and empty vector controls.

Gene→Variant (gene-first): 2050:V871I

Genes: 2050

Variants: V871I

[Paragraph-level] PMCID: PMC7294133 Section: RESULTS PassageIndex: 12

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: V871I | Summary: The EPHB4-V871I variant alters the migration properties of cells, indicating a change in molecular or biochemical function.

Gene→Variant (gene-first): 2050:V871I

Genes: 2050

Variants: V871I

[Paragraph-level] PMCID: PMC7294133 Section: RESULTS PassageIndex: 11

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: V871I | Summary: The EPHB4-V871I variant demonstrates increased migration properties in wound-healing experiments, indicating an alteration in molecular function related to cell migration. Evidence Type: Oncogenic | Mutation: V871I | Summary: The increased migration potential of EPHB4-V871I suggests that this somatic variant may contribute to tumor development or progression by enhancing cell motility.

Gene→Variant (gene-first): 2050:V871I

Genes: 2050

Variants: V871I

[Paragraph-level] PMCID: PMC7294133 Section: RESULTS PassageIndex: 10

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: V871I | Summary: The V871I mutation in EPHB4 is associated with altered cellular proliferation, as indicated by increased propagation rates in cells overexpressing this variant compared to controls. Evidence Type: Oncogenic | Mutation: V871I | Summary: The V871I mutation in EPHB4 contributes to tumor development and progression, as suggested by its involvement in increased proliferation rates in cancer cell lines.

Gene→Variant (gene-first): 2050:V871I

Genes: 2050

Variants: V871I

[Paragraph-level] PMCID: PMC7294133 Section: RESULTS PassageIndex: 9

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: V871I | Summary: The V871I mutation alters the molecular function related to the proliferation and migration of neuroblastoma (NB) cell lines.

Gene→Variant (gene-first): 2050:V871I

Genes: 2050

Variants: V871I

[Paragraph-level] PMCID: PMC7294133 Section: RESULTS PassageIndex: 8

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: V871I | Summary: The EPHB4-V871I variant was functionally characterized, showing that it does not impair EPHB4 expression at the mRNA and protein levels.

Gene→Variant (gene-first): 2050:V871I

Genes: 2050

Variants: V871I

[Paragraph-level] PMCID: PMC7294133 Section: RESULTS PassageIndex: 5

Evidence Type(s): None

Summary: Not enough information in this passage.

Gene→Variant (gene-first): 238:F1174L 2260:N457K 238:R1275Q

Genes: 238 2260

Variants: F1174L N457K R1275Q

[Paragraph-level] PMCID: PMC7294133 Section: RESULTS PassageIndex: 4

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: V871I | Summary: The variant V871I in the kinase domain of EPHB4 is associated with a high pathogenic score, indicating its contribution to tumor development or progression.

Gene→Variant (gene-first): 4613:A417S 2050:V871I

Genes: 4613 2050

Variants: A417S V871I

[Paragraph-level] PMCID: PMC7294133 Section: RESULTS PassageIndex: 3

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: F1174L | Summary: The F1174L mutation in the ALK gene is identified as a somatic variant that is frequently observed in neuroblastoma, suggesting its contribution to tumor development or progression.

Gene→Variant (gene-first): 238:F1174L

Genes: 238

Variants: F1174L

[Paragraph-level] PMCID: PMC7294133 Section: RESULTS PassageIndex: 2

Evidence Type(s): Diagnostic

Summary: Evidence Type: Diagnostic | Mutation: V871I | Summary: The EPHB4-V871I mutation is identified in neuroblastoma (NB) patients, suggesting its role in defining or classifying the disease.

Gene→Variant (gene-first): 2050:V871I

Genes: 2050

Variants: V871I

[Paper-level Aggregated] PMCID: PMC7294133

Evidence Type(s): Oncogenic, Functional, Prognostic

Justification: Oncogenic: The variant EPHB4-V871I is associated with increased proliferation, migration, and invasion properties in neuroblastoma cell lines, indicating its role in promoting tumorigenesis. Functional: The study demonstrates that EPHB4-V871I affects cellular functions such as proliferation and migration, and alters the expression of downstream target genes, confirming its functional impact in vitro. Prognostic: Higher EPHB4 expression, correlated with the EPHB4-V871I variant, is associated with advanced disease stages and poor overall survival in neuroblastoma patients.

Gene→Variant (gene-first): MYCN(4613):A417S EPHB4(2050):V871I ALK(238):F1174L

Genes: MYCN(4613) EPHB4(2050) ALK(238)

Variants: A417S V871I F1174L

[Paragraph-level] PMCID: PMC7294133 Section: ABSTRACT PassageIndex: 2

Evidence Type(s): Oncogenic, Predictive, Prognostic

Justification: Oncogenic: The variant V871I in the EPHB4 gene is described as contributing to increased proliferation, migration, and invasion properties in neuroblastoma cell lines, indicating its role in tumor development and progression. Predictive: The passage discusses the use of EPHB4 inhibitors that can rescue the phenotype driven by the variant V871I, suggesting a correlation with response to specific therapies. Prognostic: The passage mentions that higher EPHB4 expression is correlated with stage 4 neuroblastoma and poor overall survival, indicating a relationship between the variant and disease outcome.

Gene→Variant (gene-first): 2050:V871I

Genes: 2050

Variants: V871I

[Paragraph-level] PMCID: PMC7294133 Section: RESULTS PassageIndex: 16

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage indicates that treatment with TK inhibitors has a positive effect on the phenotype induced by the EPHB4-V871I variant, suggesting a correlation with response to therapy. Oncogenic: The mention of the EPHB4-V871I variant inducing a phenotype in neuroblastoma (NB) cell lines implies that it contributes to tumor development or progression.

Gene→Variant (gene-first): 2050:V871I

Genes: 2050

Variants: V871I

[Paragraph-level] PMCID: PMC7294133 Section: RESULTS PassageIndex: 15

Evidence Type(s): Functional

Justification: Functional: The passage discusses how the EPHB4-V871I variant alters the expression levels of downstream target genes and affects the phosphorylation status of the ERK1-2 pathway, indicating a change in molecular function.

Gene→Variant (gene-first): 2050:V871I

Genes: 2050

Variants: V871I

[Paragraph-level] PMCID: PMC7294133 Section: RESULTS PassageIndex: 14

Evidence Type(s): Functional

Justification: Functional: The variant V871I alters molecular function by increasing the expression of target genes and enhancing the phosphorylation of the ERK1-2 pathway.

Gene→Variant (gene-first): 2050:V871I

Genes: 2050

Variants: V871I

[Paragraph-level] PMCID: PMC7294133 Section: RESULTS PassageIndex: 13

Evidence Type(s): Oncogenic, Functional

Justification: Oncogenic: The variant EPHB4-V871I is associated with increased anchorage-independent growth, indicating its contribution to tumor development or progression as demonstrated by the colony formation assay. Functional: The passage describes the effect of the EPHB4-V871I variant on cellular behavior, specifically its impact on colony formation, which suggests an alteration in molecular or biochemical function.

Gene→Variant (gene-first): 2050:V871I

Genes: 2050

Variants: V871I

[Paragraph-level] PMCID: PMC7294133 Section: RESULTS PassageIndex: 12

Evidence Type(s): Functional

Justification: Functional: The passage discusses how the EPHB4-V871I variant alters the migration properties of cells, indicating a change in molecular function related to cell behavior.

Gene→Variant (gene-first): 2050:V871I

Genes: 2050

Variants: V871I

[Paragraph-level] PMCID: PMC7294133 Section: RESULTS PassageIndex: 11

Evidence Type(s): Functional

Justification: Functional: The passage discusses how the EPHB4-V871I variant alters the migration properties of cells, indicating a change in molecular function related to cell behavior.

Gene→Variant (gene-first): 2050:V871I

Genes: 2050

Variants: V871I

[Paragraph-level] PMCID: PMC7294133 Section: RESULTS PassageIndex: 10

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how the EPHB4-V871I variant alters the proliferation rate of cells, indicating a change in molecular or biochemical function. Oncogenic: The increased proliferation rate associated with the EPHB4-V871I variant suggests its contribution to tumor development or progression, as it is linked to cellular behaviors relevant to cancer.

Gene→Variant (gene-first): 2050:V871I

Genes: 2050

Variants: V871I

[Paragraph-level] PMCID: PMC7294133 Section: RESULTS PassageIndex: 9

Evidence Type(s): Functional

Justification: Functional: The passage indicates that EPHB4-V871I alters the proliferation and migration of neuroblastoma (NB) cell lines, suggesting a change in molecular or biochemical function.

Gene→Variant (gene-first): 2050:V871I

Genes: 2050

Variants: V871I

[Paragraph-level] PMCID: PMC7294133 Section: RESULTS PassageIndex: 8

Evidence Type(s): Functional

Justification: Functional: The passage discusses the functional characterization of the EPHB4-V871I variant, specifically evaluating its expression and confirming that the mutation does not impair EPHB4 expression at the mRNA and protein level.

Gene→Variant (gene-first): 2050:V871I

Genes: 2050

Variants: V871I

[Paragraph-level] PMCID: PMC7294133 Section: RESULTS PassageIndex: 5

Evidence Type(s): None

Justification: Not enough information in this passage.

Gene→Variant (gene-first): 238:F1174L 2260:N457K 238:R1275Q

Genes: 238 2260

Variants: F1174L N457K R1275Q

[Paragraph-level] PMCID: PMC7294133 Section: RESULTS PassageIndex: 4

Evidence Type(s): Oncogenic, Functional

Justification: Oncogenic: The passage discusses mutations in EPHB4 and EphB6 genes, indicating that the variant V871I is associated with a high pathogenic score, suggesting its contribution to tumor development or progression. Functional: The mention of the variant V871I being located in the kinase domain of EPHB4 implies a potential alteration in molecular or biochemical function related to its role in the axon guidance pathway.

Gene→Variant (gene-first): 4613:A417S 2050:V871I

Genes: 4613 2050

Variants: A417S V871I

[Paragraph-level] PMCID: PMC7294133 Section: RESULTS PassageIndex: 3

Evidence Type(s): Oncogenic

Justification: Oncogenic: The passage indicates that the variant F1174L is a somatic mutation found in the ALK gene, which is associated with neuroblastoma (NB), suggesting its contribution to tumor development or progression.

Gene→Variant (gene-first): 238:F1174L

Genes: 238

Variants: F1174L

[Paragraph-level] PMCID: PMC7294133 Section: RESULTS PassageIndex: 2

Evidence Type(s): None

Justification: Not enough information in this passage.

Gene→Variant (gene-first): 2050:V871I

Genes: 2050

Variants: V871I

[Paragraph-level] PMCID: PMC7294133 Section: RESULTS PassageIndex: 16

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage indicates that treatment with TK inhibitors has a positive effect on the phenotype induced by the EPHB4-V871I variant, suggesting a correlation with response to therapy. Oncogenic: The mention of the EPHB4-V871I variant inducing a phenotype in neuroblastoma (NB) cell lines implies that it contributes to tumor development or progression.

Gene→Variant (gene-first): 2050:V871I

Genes: 2050

Variants: V871I

[Paragraph-level] PMCID: PMC7294133 Section: RESULTS PassageIndex: 15

Evidence Type(s): Functional

Justification: Functional: The passage discusses how the EPHB4-V871I variant alters the expression levels of downstream target genes and affects the phosphorylation status of the ERK1-2 pathway, indicating a change in molecular function.

Gene→Variant (gene-first): 2050:V871I

Genes: 2050

Variants: V871I

[Paragraph-level] PMCID: PMC7294133 Section: RESULTS PassageIndex: 14

Evidence Type(s): Functional

Justification: Functional: The variant V871I alters molecular function by increasing the expression of target genes and enhancing the phosphorylation of the ERK1-2 pathway.

Gene→Variant (gene-first): 2050:V871I

Genes: 2050

Variants: V871I

[Paragraph-level] PMCID: PMC7294133 Section: RESULTS PassageIndex: 13

Evidence Type(s): Oncogenic, Functional

Justification: Oncogenic: The variant EPHB4-V871I is associated with increased anchorage-independent growth, indicating its contribution to tumor development or progression as demonstrated by the colony formation assay. Functional: The passage describes the effect of the EPHB4-V871I variant on cellular behavior, specifically its impact on colony formation, which suggests an alteration in molecular or biochemical function.

Gene→Variant (gene-first): 2050:V871I

Genes: 2050

Variants: V871I

[Paragraph-level] PMCID: PMC7294133 Section: RESULTS PassageIndex: 12

Evidence Type(s): Functional

Justification: Functional: The passage discusses how the EPHB4-V871I variant alters the migration properties of cells, indicating a change in molecular function related to cell behavior.

Gene→Variant (gene-first): 2050:V871I

Genes: 2050

Variants: V871I

[Paragraph-level] PMCID: PMC7294133 Section: RESULTS PassageIndex: 11

Evidence Type(s): Functional

Justification: Functional: The passage discusses how the EPHB4-V871I variant alters the migration properties of cells, indicating a change in molecular function related to cell behavior.

Gene→Variant (gene-first): 2050:V871I

Genes: 2050

Variants: V871I

[Paragraph-level] PMCID: PMC7294133 Section: RESULTS PassageIndex: 10

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how the EPHB4-V871I variant alters the proliferation rate of cells, indicating a change in molecular or biochemical function. Oncogenic: The increased proliferation rate associated with the EPHB4-V871I variant suggests its contribution to tumor development or progression, as it is linked to cellular behaviors relevant to cancer.

Gene→Variant (gene-first): 2050:V871I

Genes: 2050

Variants: V871I

[Paragraph-level] PMCID: PMC7294133 Section: RESULTS PassageIndex: 9

Evidence Type(s): Functional

Justification: Functional: The passage indicates that EPHB4-V871I alters the proliferation and migration of neuroblastoma (NB) cell lines, suggesting a change in molecular or biochemical function.

Gene→Variant (gene-first): 2050:V871I

Genes: 2050

Variants: V871I

[Paragraph-level] PMCID: PMC7294133 Section: RESULTS PassageIndex: 8

Evidence Type(s): Functional

Justification: Functional: The passage discusses the functional characterization of the EPHB4-V871I variant, specifically evaluating its expression and confirming that the mutation does not impair EPHB4 expression at the mRNA and protein level.

Gene→Variant (gene-first): 2050:V871I

Genes: 2050

Variants: V871I

[Paragraph-level] PMCID: PMC7294133 Section: RESULTS PassageIndex: 5

Evidence Type(s): None

Justification: Not enough information in this passage.

Gene→Variant (gene-first): 238:F1174L 2260:N457K 238:R1275Q

Genes: 238 2260

Variants: F1174L N457K R1275Q

[Paragraph-level] PMCID: PMC7294133 Section: RESULTS PassageIndex: 4

Evidence Type(s): Oncogenic, Functional

Justification: Oncogenic: The passage discusses mutations in EPHB4 and EphB6 genes, indicating that the variant V871I is associated with a high pathogenic score, suggesting its contribution to tumor development or progression. Functional: The mention of the variant V871I being located in the kinase domain of EPHB4 implies a potential alteration in molecular or biochemical function related to its role in the axon guidance pathway.

Gene→Variant (gene-first): 4613:A417S 2050:V871I

Genes: 4613 2050

Variants: A417S V871I

[Paragraph-level] PMCID: PMC7294133 Section: RESULTS PassageIndex: 3

Evidence Type(s): Oncogenic

Justification: Oncogenic: The passage indicates that the variant F1174L is a somatic mutation found in the ALK gene, which is associated with neuroblastoma (NB), suggesting its contribution to tumor development or progression.

Gene→Variant (gene-first): 238:F1174L

Genes: 238

Variants: F1174L

[Paragraph-level] PMCID: PMC7294133 Section: RESULTS PassageIndex: 2

Evidence Type(s): None

Justification: Not enough information in this passage.

Gene→Variant (gene-first): 2050:V871I

Genes: 2050

Variants: V871I