[Paper-level Aggregated] PMCID: PMC3366948

Evidence Type(s): Functional

Summary: Mutation: A35V | Summary: The A35V variant was present in the CCRF-CEM cell line and one additional clone, but analysis could not identify major differences in transforming properties compared to wild type TYK2.

Evidence Type: Functional Mutation: C192Y | Summary: The C192Y mutation was only found in the JURKAT line and was absent in other clones, with no significant differences in autophosphorylation observed compared to wild type TYK2.

Gene→Variant (gene-first): MST1R(4486):A35V PMS2(5395):C192Y

Genes: MST1R(4486) PMS2(5395)

Variants: A35V C192Y

[Paper-level Aggregated] PMCID: PMC3366948

Evidence Type(s): Oncogenic

Summary: Mutation: A572T | Summary: The A572T mutation in JAK3 is described as a somatic mutation that contributes to tumor development, as it was detected in T-ALL and associated with leukemia induction in mice.

Evidence Type: Oncogenic Mutation: M511I | Summary: The M511I mutation in JAK3 is a somatic mutation that has been previously associated with AML and has been shown to transform IL3 dependent cells and induce T-ALL in mice.

Evidence Type: Oncogenic Mutation: A572V | Summary: The A572V mutation in JAK3 is noted to be a somatic variant that has been implicated in T-cell leukemia, T-cell lymphoma, and AML, contributing to tumor development by transforming hematopoietic cells and inducing leukemia in mice.

Evidence Type: Oncogenic Mutation: H1297Y | Summary: The H1297Y variant in TET1 is confirmed as a somatic mutation associated with tumor development in T-ALL, as indicated by its presence in a remission sample.

Evidence Type: Oncogenic Mutation: R1027H | Summary: The R1027H variant was present in all analyzed samples, but the data suggest that it may not represent an oncogenic event important for leukemia development in vivo.

Gene→Variant (gene-first): JAK3(3718):A572T JAK3(3718):M511I JAK3(3718):A572V TET1(80312):H1297Y TYK2(7297):R1027H

Genes: JAK3(3718) TET1(80312) TYK2(7297)

Variants: A572T M511I A572V H1297Y R1027H

[Paragraph-level] PMCID: PMC3366948 Section: RESULTS PassageIndex: 22

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: R1027H | Summary: The R1027H variant was present in all analyzed samples, but the data suggest that it may not represent an oncogenic event important for leukemia development in vivo. Evidence Type: Functional | Mutation: A35V | Summary: The A35V variant was present in the CCRF-CEM cell line and one additional clone, but analysis could not identify major differences in transforming properties compared to wild type TYK2. Evidence Type: Functional | Mutation: C192Y | Summary: The C192Y mutation was only found in the JURKAT line and was absent in other clones, with no significant differences in autophosphorylation observed compared to wild type TYK2.

Gene→Variant (gene-first): 4486:A35V 5395:C192Y 7297:R1027H

Genes: 4486 5395 7297

Variants: A35V C192Y R1027H

[Paragraph-level] PMCID: PMC3366948 Section: RESULTS PassageIndex: 18

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: H1297Y | Summary: The H1297Y variant in TET1 is confirmed as a somatic mutation associated with tumor development in T-ALL, as indicated by its presence in a remission sample.

Gene→Variant (gene-first): 80312:H1297Y

Genes: 80312

Variants: H1297Y

[Paragraph-level] PMCID: PMC3366948 Section: RESULTS PassageIndex: 15

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: A572T | Summary: The A572T mutation in JAK3 is described as a somatic mutation that contributes to tumor development, as it was detected in T-ALL and associated with leukemia induction in mice. Evidence Type: Oncogenic | Mutation: M511I | Summary: The M511I mutation in JAK3 is a somatic mutation that has been previously associated with AML and has been shown to transform IL3 dependent cells and induce T-ALL in mice. Evidence Type: Oncogenic | Mutation: A572V | Summary: The A572V mutation in JAK3 is noted to be a somatic variant that has been implicated in T-cell leukemia, T-cell lymphoma, and AML, contributing to tumor development by transforming hematopoietic cells and inducing leukemia in mice.

Gene→Variant (gene-first): 3718:A572 3718:A572T 3718:A572V 3718:M511I

Genes: 3718

Variants: A572 A572T A572V M511I

[Paper-level Aggregated] PMCID: PMC3366948

Evidence Type(s): Oncogenic, Functional, Predisposing, Diagnostic, Prognostic

Justification: Oncogenic: The text states that JAK2 and JAK3 are known oncogenes in leukemia, and specific mutations such as M511I and A572V have been shown to induce leukemia in mice, indicating their oncogenic potential. Functional: The M511I mutation was shown to transform IL3 dependent 32D cells and induce T-ALL in mice, demonstrating a functional impact on cellular behavior. Predisposing: The presence of mutations in JAK2 and JAK3 in T-ALL patients suggests a predisposition to developing this type of leukemia, as these mutations were identified in patient samples. Diagnostic: The identification of specific mutations in JAK2 and JAK3 in T-ALL patients can serve as diagnostic markers for the disease, as indicated by their presence in patient samples. Prognostic: The somatic status of the H1297Y variant in TET1, confirmed in a remission sample, suggests that it may have implications for prognosis in T-ALL patients.

Gene→Variant (gene-first): MST1R(4486):A35V PMS2(5395):C192Y TYK2(7297):R1027H JAK3(3718):A572 JAK3(3718):A572T JAK3(3718):A572V JAK3(3718):M511I TET1(80312):H1297Y

Genes: MST1R(4486) PMS2(5395) TYK2(7297) JAK3(3718) TET1(80312)

Variants: A35V C192Y R1027H A572 A572T A572V M511I H1297Y

[Paragraph-level] PMCID: PMC3366948 Section: RESULTS PassageIndex: 22

Evidence Type(s): Oncogenic, Functional

Justification: Oncogenic: The passage discusses the presence of TYK2 mutations in T-ALL cell lines and suggests that these mutations may not represent an oncogenic event important for leukemia development in vivo, indicating a potential role in tumor progression. Functional: The analysis of the transforming properties of the TYK2 variants in Ba/F3 cells indicates that the variants do not show major differences in function compared to wild type TYK2, suggesting an assessment of molecular function.

Gene→Variant (gene-first): 4486:A35V 5395:C192Y 7297:R1027H

Genes: 4486 5395 7297

Variants: A35V C192Y R1027H

[Paragraph-level] PMCID: PMC3366948 Section: RESULTS PassageIndex: 18

Evidence Type(s): Oncogenic

Justification: Oncogenic: The variant H1297Y is described as a somatic variant confirmed in a patient case, indicating its contribution to tumor development or progression in the context of T-ALL.

Gene→Variant (gene-first): 80312:H1297Y

Genes: 80312

Variants: H1297Y

[Paragraph-level] PMCID: PMC3366948 Section: RESULTS PassageIndex: 15

Evidence Type(s): Oncogenic, Functional

Justification: Oncogenic: The passage describes that the M511I mutation transformed IL3 dependent 32D cells and induced T-ALL in mice, indicating its role in tumor development. Additionally, the A572V mutation was shown to transform cytokine dependent hematopoietic cells and induce leukemia in mice, further supporting its oncogenic potential. Functional: The passage discusses how specific mutations in JAK3, such as A572T and A572V, alter the function of the protein, as evidenced by their ability to transform cells and induce leukemia, indicating a change in molecular or biochemical function.

Gene→Variant (gene-first): 3718:A572 3718:A572T 3718:A572V 3718:M511I

Genes: 3718

Variants: A572 A572T A572V M511I

[Paragraph-level] PMCID: PMC3366948 Section: RESULTS PassageIndex: 22

Evidence Type(s): Oncogenic, Functional

Justification: Oncogenic: The passage discusses the presence of TYK2 mutations in T-ALL cell lines and suggests that these mutations may not represent an oncogenic event important for leukemia development in vivo, indicating a potential role in tumor progression. Functional: The analysis of the transforming properties of the TYK2 variants in Ba/F3 cells indicates that the variants do not show major differences in function compared to wild type TYK2, suggesting an assessment of molecular function.

Gene→Variant (gene-first): 4486:A35V 5395:C192Y 7297:R1027H

Genes: 4486 5395 7297

Variants: A35V C192Y R1027H

[Paragraph-level] PMCID: PMC3366948 Section: RESULTS PassageIndex: 18

Evidence Type(s): Oncogenic

Justification: Oncogenic: The variant H1297Y is described as a somatic variant confirmed in a patient case, indicating its contribution to tumor development or progression in the context of T-ALL.

Gene→Variant (gene-first): 80312:H1297Y

Genes: 80312

Variants: H1297Y

[Paragraph-level] PMCID: PMC3366948 Section: RESULTS PassageIndex: 15

Evidence Type(s): Oncogenic, Functional

Justification: Oncogenic: The passage describes that the M511I mutation transformed IL3 dependent 32D cells and induced T-ALL in mice, indicating its role in tumor development. Additionally, the A572V mutation was shown to transform cytokine dependent hematopoietic cells and induce leukemia in mice, further supporting its oncogenic potential. Functional: The passage discusses how specific mutations in JAK3, such as A572T and A572V, alter the function of the protein, as evidenced by their ability to transform cells and induce leukemia, indicating a change in molecular or biochemical function.

Gene→Variant (gene-first): 3718:A572 3718:A572T 3718:A572V 3718:M511I

Genes: 3718

Variants: A572 A572T A572V M511I