[Paper-level Aggregated] PMCID: PMC4868698

Evidence Type(s): Functional

Summary: Mutation: E483D | Summary: The JAK1E483D mutation is part of a study evaluating the transformation ability of JAK1 mutations, indicating a potential alteration in molecular function.

Evidence Type: Functional Mutation: S703I | Summary: The JAK1S703I mutation alters the molecular function by activating the JAK-STAT signaling pathway and driving cell proliferation in vitro, contributing to tumor development by enabling continual proliferation in the absence of IL-3.

Gene→Variant (gene-first): JAK1(3716):E483D JAK1(3716):S703I

Genes: JAK1(3716)

Variants: E483D S703I

[Paper-level Aggregated] PMCID: PMC4868698

Evidence Type(s): Oncogenic

Summary: Mutation: S703I | Summary: The JAK1S703I mutation is identified as an activating mutation contributing to tumor development in HCC patients. It is associated with elevated expression levels of phosphorylated JAK1 and STAT proteins, suggesting its role in tumor progression. The mutation is capable of continual proliferation in the absence of IL-3 and is present in a patient-derived xenograft (PDX) model, indicating its critical role in tumorigenesis. Additionally, it activates the JAK-STAT signaling pathway, driving cell proliferation in vitro.

Evidence Type: Oncogenic Mutation: A1086S | Summary: The A1086S mutation is located in the catalytic kinase domain of JAK1, suggesting its role in tumor development.

Evidence Type: Oncogenic Mutation: N451S | Summary: The N451S mutation is found in the SH2 domain of JAK1, indicating its potential contribution to tumor progression.

Evidence Type: Oncogenic Mutation: E483D | Summary: The E483D mutation, located in the SH2 domain of JAK1, may play a role in tumor development. It is part of a study exploring biological functions in the JAK-STAT signaling pathway, indicating its potential role in tumor development.

Evidence Type: Oncogenic Mutation: S729C | Summary: The JAK1S729C mutation is described as a known and recurrent activating mutation, indicating its role in tumor development. It serves as a positive control in studies, suggesting it contributes to continual proliferation and tumor progression.

Gene→Variant (gene-first): JAK1(3716):S703I JAK1(3716):A1086S POTEF(728378):N451S JAK1(3716):E483D JAK1(3716):S729C

Genes: JAK1(3716) POTEF(728378)

Variants: S703I A1086S N451S E483D S729C

[Paper-level Aggregated] PMCID: PMC4868698

Evidence Type(s): Predictive

Summary: Mutation: S703I | Summary: The S703I mutation in JAK1 correlates with sensitivity to the JAK1/2 inhibitor ruxolitinib and is associated with a response to this therapy, indicating its potential predictive value for treatment outcomes and therapy sensitivity.

Gene→Variant (gene-first): JAK1(3716):S703I

Genes: JAK1(3716)

Variants: S703I

[Paragraph-level] PMCID: PMC4868698 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Functional, Predictive, Oncogenic

Summary: Evidence Type: Functional | Mutation: S703I | Summary: The JAK1S703I mutation alters the molecular function by activating the JAK-STAT signaling pathway and driving cell proliferation in vitro. Evidence Type: Predictive | Mutation: S703I | Summary: The JAK1S703I mutation correlates with sensitivity to the JAK1/2 inhibitor ruxolitinib, indicating its potential as a predictive biomarker for therapy response in HCC. Evidence Type: Oncogenic | Mutation: S703I | Summary: The JAK1S703I mutation contributes to tumor development by activating the JAK-STAT signaling pathway, which is associated with cell proliferation in the absence of cytokine stimulation.

Gene→Variant (gene-first): 3716:S703I

Genes: 3716

Variants: S703I

[Paragraph-level] PMCID: PMC4868698 Section: RESULTS PassageIndex: 14

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: S703I | Summary: The S703I mutation in JAK1 is associated with a response to ruxolitinib treatment, indicating its potential predictive value for therapy sensitivity. Evidence Type: Oncogenic | Mutation: S703I | Summary: The presence of the S703I mutation in JAK1 suggests its contribution to tumor development or progression, highlighting its oncogenic potential.

Gene→Variant (gene-first): 3716:S703I

Genes: 3716

Variants: S703I

[Paragraph-level] PMCID: PMC4868698 Section: RESULTS PassageIndex: 11

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: S703I | Summary: The JAK1S703I mutation correlates with sensitivity to the JAK1/2 inhibitor ruxolitinib, indicating its potential role in predicting treatment response. Evidence Type: Oncogenic | Mutation: S703I | Summary: The JAK1S703I mutation is suggested to play a critical role in tumorigenesis in the LI-03-0191 PDX model, indicating its contribution to tumor development.

Gene→Variant (gene-first): 3716:S703I

Genes: 3716

Variants: S703I

[Paragraph-level] PMCID: PMC4868698 Section: RESULTS PassageIndex: 10

Evidence Type(s): Oncogenic, Predictive

Summary: Evidence Type: Oncogenic | Mutation: S703I | Summary: The S703I mutation in JAK1 is associated with tumor development or progression, as indicated by its presence in a patient-derived xenograft (PDX) model. Evidence Type: Predictive | Mutation: S703I | Summary: The S703I mutation correlates with the response to the therapy ruxolitinib, suggesting its predictive value in treatment outcomes.

Gene→Variant (gene-first): 3716:S703I

Genes: 3716

Variants: S703I

[Paragraph-level] PMCID: PMC4868698 Section: RESULTS PassageIndex: 9

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: E483D | Summary: The JAK1E483D mutation is part of a study evaluating the transformation ability of JAK1 mutations, indicating a potential alteration in molecular function. Evidence Type: Oncogenic | Mutation: S703I | Summary: The JAK1S703I mutation is capable of continual proliferation in the absence of IL-3, suggesting it contributes to tumor development or progression. Evidence Type: Oncogenic | Mutation: S729C | Summary: The JAK1S729C mutation serves as a positive control in the study, indicating its role in enabling continual proliferation and suggesting it contributes to tumor development or progression.

Gene→Variant (gene-first): 3716:E483D 3716:S703I 3716:S729C

Genes: 3716

Variants: E483D S703I S729C

[Paragraph-level] PMCID: PMC4868698 Section: RESULTS PassageIndex: 8

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: E483D | Summary: The JAK1E483D mutation is part of a study exploring biological functions in the JAK-STAT signaling pathway, indicating its potential role in tumor development. Evidence Type: Oncogenic | Mutation: S703I | Summary: The JAK1S703I mutation is associated with elevated expression levels of phosphorylated JAK1 and STAT proteins, suggesting its contribution to tumor progression. Evidence Type: Oncogenic | Mutation: S729C | Summary: The JAK1S729C mutation is described as a known and recurrent activating mutation, indicating its role in tumor development.

Gene→Variant (gene-first): 3716:E483D 3716:S703I 3716:S729C

Genes: 3716

Variants: E483D S703I S729C

[Paragraph-level] PMCID: PMC4868698 Section: RESULTS PassageIndex: 4

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: S703I | Summary: The S703I mutation is identified as an activating mutation of the JAK1 gene, contributing to tumor development in HCC patients. Evidence Type: Oncogenic | Mutation: A1086S | Summary: The A1086S mutation is located in the catalytic kinase domain of JAK1, suggesting its role in tumor development. Evidence Type: Oncogenic | Mutation: N451S | Summary: The N451S mutation is found in the SH2 domain of JAK1, indicating its potential contribution to tumor progression. Evidence Type: Oncogenic | Mutation: E483D | Summary: The E483D mutation, located in the SH2 domain of JAK1, may also play a role in tumor development.

Gene→Variant (gene-first): 3716:A1086S 3716:E483D 728378:N451S 3716:S703I

Genes: 3716 728378

Variants: A1086S E483D N451S S703I

[Paragraph-level] PMCID: PMC4868698 Section: RESULTS PassageIndex: 3

Evidence Type(s): None

Summary: Not enough information in this passage.

Gene→Variant (gene-first): 3716:A1086S 3716:E483D 728378:N451S 3716:S703I

Genes: 3716 728378

Variants: A1086S E483D N451S S703I

[Paper-level Aggregated] PMCID: PMC4868698

Evidence Type(s): Oncogenic, Functional, Prognostic

Justification: Oncogenic: The S703I mutation is described as an activating mutation of the JAK1 gene, which drives cell proliferation and activates the JAK-STAT signaling pathway, indicating its role in tumorigenesis. Functional: The introduction of the S703I mutation into cell lines demonstrated its ability to activate the JAK-STAT signaling pathway and promote cell proliferation, showcasing its functional impact on cellular behavior. Prognostic: The sensitivity of the JAK1S703I mutant PDX model to ruxolitinib treatment suggests that this mutation may serve as a prognostic marker for response to targeted therapies in hepatocellular carcinoma.

Gene→Variant (gene-first): JAK1(3716):A1086S JAK1(3716):E483D POTEF(728378):N451S JAK1(3716):S703I JAK1(3716):S729C

Genes: JAK1(3716) POTEF(728378)

Variants: A1086S E483D N451S S703I S729C

[Paragraph-level] PMCID: PMC4868698 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the sensitivity of the JAK1S703I mutant PDX model to the treatment of a JAK1/2 inhibitor, ruxolitinib, indicating a correlation with response to therapy. Oncogenic: The JAK1S703I mutation is described as activating the JAK-STAT signaling pathway and driving cell proliferation, which suggests its contribution to tumor development or progression.

Gene→Variant (gene-first): 3716:S703I

Genes: 3716

Variants: S703I

[Paragraph-level] PMCID: PMC4868698 Section: RESULTS PassageIndex: 14

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the treatment of ruxolitinib and its effects on the phosphorylation level of STAT3 in tumors with the JAK1 S703I mutation, indicating a correlation with treatment response. Oncogenic: The mention of the JAK1 S703I mutation in the context of tumor models suggests that this somatic variant contributes to tumor development or progression.

Gene→Variant (gene-first): 3716:S703I

Genes: 3716

Variants: S703I

[Paragraph-level] PMCID: PMC4868698 Section: RESULTS PassageIndex: 11

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the sensitivity of the JAK1S703I mutation to the JAK1/2 inhibitor ruxolitinib, indicating a correlation with treatment response. Oncogenic: The passage suggests that the JAK1S703I mutation may play a critical role in tumorigenesis, indicating its contribution to tumor development.

Gene→Variant (gene-first): 3716:S703I

Genes: 3716

Variants: S703I

[Paragraph-level] PMCID: PMC4868698 Section: RESULTS PassageIndex: 10

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the anti-tumor activity of ruxolitinib in a model with the JAK1 S703I mutation, indicating a correlation with response to therapy. Oncogenic: The mention of the JAK1 S703I mutation in the context of a PDX model suggests that this somatic variant contributes to tumor development or progression.

Gene→Variant (gene-first): 3716:S703I

Genes: 3716

Variants: S703I

[Paragraph-level] PMCID: PMC4868698 Section: RESULTS PassageIndex: 9

Evidence Type(s): Oncogenic, Functional

Justification: Oncogenic: The passage discusses the transformation ability of JAK1 mutations, specifically noting that JAK1S703I and JAK1S729C are capable of continual proliferation in the absence of IL-3, indicating their contribution to tumor development or progression. Functional: The passage mentions that JAK1S703I activates the JAK-STAT signaling pathway, which indicates an alteration in molecular function related to the variant.

Gene→Variant (gene-first): 3716:E483D 3716:S703I 3716:S729C

Genes: 3716

Variants: E483D S703I S729C

[Paragraph-level] PMCID: PMC4868698 Section: RESULTS PassageIndex: 8

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how the introduction of JAK1 mutations, including E483D, S703I, and S729C, alters the expression levels of phosphorylated JAK1 and STAT proteins, indicating a change in molecular function. Oncogenic: The passage mentions that JAK1S729C is a known and recurrent activating mutation, suggesting its role in tumor development or progression.

Gene→Variant (gene-first): 3716:E483D 3716:S703I 3716:S729C

Genes: 3716

Variants: E483D S703I S729C

[Paragraph-level] PMCID: PMC4868698 Section: RESULTS PassageIndex: 4

Evidence Type(s): Oncogenic, Functional

Justification: Oncogenic: The passage indicates that the S703I mutation is an activating mutation of the JAK1 gene and was found in tumors, suggesting it contributes to tumor development or progression. Functional: The S703I mutation is described as potentially causing disruption of auto-inhibition of the JAK1 kinase, indicating an alteration in molecular or biochemical function.

Gene→Variant (gene-first): 3716:A1086S 3716:E483D 728378:N451S 3716:S703I

Genes: 3716 728378

Variants: A1086S E483D N451S S703I

[Paragraph-level] PMCID: PMC4868698 Section: RESULTS PassageIndex: 3

Evidence Type(s): None

Justification: Not enough information in this passage.

Gene→Variant (gene-first): 3716:A1086S 3716:E483D 728378:N451S 3716:S703I

Genes: 3716 728378

Variants: A1086S E483D N451S S703I

[Paragraph-level] PMCID: PMC4868698 Section: RESULTS PassageIndex: 14

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the treatment of ruxolitinib and its effects on the phosphorylation level of STAT3 in tumors with the JAK1 S703I mutation, indicating a correlation with treatment response. Oncogenic: The mention of the JAK1 S703I mutation in the context of tumor models suggests that this somatic variant contributes to tumor development or progression.

Gene→Variant (gene-first): 3716:S703I

Genes: 3716

Variants: S703I

[Paragraph-level] PMCID: PMC4868698 Section: RESULTS PassageIndex: 11

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the sensitivity of the JAK1S703I mutation to the JAK1/2 inhibitor ruxolitinib, indicating a correlation with treatment response. Oncogenic: The passage suggests that the JAK1S703I mutation may play a critical role in tumorigenesis, indicating its contribution to tumor development.

Gene→Variant (gene-first): 3716:S703I

Genes: 3716

Variants: S703I

[Paragraph-level] PMCID: PMC4868698 Section: RESULTS PassageIndex: 10

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the anti-tumor activity of ruxolitinib in a model with the JAK1 S703I mutation, indicating a correlation with response to therapy. Oncogenic: The mention of the JAK1 S703I mutation in the context of a PDX model suggests that this somatic variant contributes to tumor development or progression.

Gene→Variant (gene-first): 3716:S703I

Genes: 3716

Variants: S703I

[Paragraph-level] PMCID: PMC4868698 Section: RESULTS PassageIndex: 9

Evidence Type(s): Oncogenic, Functional

Justification: Oncogenic: The passage discusses the transformation ability of JAK1 mutations, specifically noting that JAK1S703I and JAK1S729C are capable of continual proliferation in the absence of IL-3, indicating their contribution to tumor development or progression. Functional: The passage mentions that JAK1S703I activates the JAK-STAT signaling pathway, which indicates an alteration in molecular function related to the variant.

Gene→Variant (gene-first): 3716:E483D 3716:S703I 3716:S729C

Genes: 3716

Variants: E483D S703I S729C

[Paragraph-level] PMCID: PMC4868698 Section: RESULTS PassageIndex: 8

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how the introduction of JAK1 mutations, including E483D, S703I, and S729C, alters the expression levels of phosphorylated JAK1 and STAT proteins, indicating a change in molecular function. Oncogenic: The passage mentions that JAK1S729C is a known and recurrent activating mutation, suggesting its role in tumor development or progression.

Gene→Variant (gene-first): 3716:E483D 3716:S703I 3716:S729C

Genes: 3716

Variants: E483D S703I S729C

[Paragraph-level] PMCID: PMC4868698 Section: RESULTS PassageIndex: 4

Evidence Type(s): Oncogenic, Functional

Justification: Oncogenic: The passage indicates that the S703I mutation is an activating mutation of the JAK1 gene and was found in tumors, suggesting it contributes to tumor development or progression. Functional: The S703I mutation is described as potentially causing disruption of auto-inhibition of the JAK1 kinase, indicating an alteration in molecular or biochemical function.

Gene→Variant (gene-first): 3716:A1086S 3716:E483D 728378:N451S 3716:S703I

Genes: 3716 728378

Variants: A1086S E483D N451S S703I

[Paragraph-level] PMCID: PMC4868698 Section: RESULTS PassageIndex: 3

Evidence Type(s): None

Justification: Not enough information in this passage.

Gene→Variant (gene-first): 3716:A1086S 3716:E483D 728378:N451S 3716:S703I

Genes: 3716 728378

Variants: A1086S E483D N451S S703I