[Paper-level Aggregated] PMCID: PMC10283448

Evidence Type(s): Oncogenic, Functional

Justification: Oncogenic: The presence of the ROS1-G2032R mutation is associated with crizotinib resistance in lung cancer, indicating its role in tumor progression and treatment failure. Functional: The study investigates the functional impact of various mutations, including E253Q, H178Q, H179Y, H555R, R143Q, and E171G, in the context of acquired resistance to repotrectinib, suggesting their potential roles in tumor biology and treatment response.

Gene→Variant (gene-first): CEBPA(1050):196_197insHP TP53(7157):E171G CCND3(896):E253Q ERBB2(2064):H178Q TP53(7157):H179Y RB1(5925):H555R ERBB2(2064):R143Q ROS1(6098):G2032R

Genes: CEBPA(1050) TP53(7157) CCND3(896) ERBB2(2064) RB1(5925) ROS1(6098)

Variants: 196_197insHP E171G E253Q H178Q H179Y H555R R143Q G2032R

[Paragraph-level] PMCID: PMC10283448 Section: RESULTS PassageIndex: 14

Evidence Type(s): Predictive, Functional

Justification: Predictive: The passage discusses mutations identified in patients who progressed on repotrectinib treatment, suggesting a potential role of these variants in acquired resistance to the therapy. Functional: The passage indicates that further studies are necessary to investigate the functional role of the mutations, implying that these variants may alter molecular or biochemical functions related to resistance mechanisms.

Gene→Variant (gene-first): 1050:196_197insHP 7157:E171G 896:E253Q 2064:H178Q 7157:H179Y 5925:H555R 2064:R143Q

Genes: 1050 7157 896 2064 5925

Variants: 196_197insHP E171G E253Q H178Q H179Y H555R R143Q

[Paragraph-level] PMCID: PMC10283448 Section: RESULTS PassageIndex: 12

Evidence Type(s): Predictive, Diagnostic

Justification: Predictive: The passage discusses the clinical activity of repotrectinib in a patient with the G2032R mutation, indicating a response to therapy, which aligns with predictive evidence. Diagnostic: The G2032R mutation is identified in the context of a ROS1-rearranged patient, suggesting its role in defining the patient's disease subtype.

Gene→Variant (gene-first): 6098:G2032R

Genes: 6098

Variants: G2032R

[Paragraph-level] PMCID: PMC10283448 Section: RESULTS PassageIndex: 10

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the response of the ROS1-G2032R mutation to various therapies, specifically mentioning the effectiveness of cabozantinib and repotrectinib in inhibiting growth, which correlates with treatment response. Oncogenic: The ROS1-G2032R mutation is implicated in tumor growth, as indicated by the investigation of its effects in Ba/F3 cells and the context of progression on crizotinib treatment, suggesting its role in tumor development.

Gene→Variant (gene-first): 6098:G2032R

Genes: 6098

Variants: G2032R

[Paragraph-level] PMCID: PMC10283448 Section: RESULTS PassageIndex: 9

Evidence Type(s): Predictive

Justification: Predictive: The passage indicates that repotrectinib is effective against crizotinib-resistant ROS1 G2032R, suggesting a correlation between the variant and response to therapy.

Gene→Variant (gene-first): 6098:G2032R

Genes: 6098

Variants: G2032R

[Paragraph-level] PMCID: PMC10283448 Section: ABSTRACT PassageIndex: 2

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the high prevalence of the crizotinib-resistant ROS1-G2032R mutation and its implications for treatment response, indicating a correlation with resistance to therapy. Oncogenic: The mention of the ROS1-G2032R mutation in the context of crizotinib resistance suggests that it contributes to tumor progression, which aligns with the definition of an oncogenic variant.

Gene→Variant (gene-first): 6098:G2032R

Genes: 6098

Variants: G2032R

[Paragraph-level] PMCID: PMC10283448 Section: RESULTS PassageIndex: 14

Evidence Type(s): Predictive, Functional

Justification: Predictive: The passage discusses mutations identified in patients who progressed on repotrectinib treatment, suggesting a potential role of these variants in acquired resistance to the therapy. Functional: The passage indicates that further studies are necessary to investigate the functional role of the mutations, implying that these variants may alter molecular or biochemical functions related to resistance mechanisms.

Gene→Variant (gene-first): 1050:196_197insHP 7157:E171G 896:E253Q 2064:H178Q 7157:H179Y 5925:H555R 2064:R143Q

Genes: 1050 7157 896 2064 5925

Variants: 196_197insHP E171G E253Q H178Q H179Y H555R R143Q

[Paragraph-level] PMCID: PMC10283448 Section: RESULTS PassageIndex: 12

Evidence Type(s): Predictive, Diagnostic

Justification: Predictive: The passage discusses the clinical activity of repotrectinib in a patient with the G2032R mutation, indicating a response to therapy, which aligns with predictive evidence. Diagnostic: The G2032R mutation is identified in the context of a ROS1-rearranged patient, suggesting its role in defining the patient's disease subtype.

Gene→Variant (gene-first): 6098:G2032R

Genes: 6098

Variants: G2032R

[Paragraph-level] PMCID: PMC10283448 Section: RESULTS PassageIndex: 10

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the response of the ROS1-G2032R mutation to various therapies, specifically mentioning the effectiveness of cabozantinib and repotrectinib in inhibiting growth, which correlates with treatment response. Oncogenic: The ROS1-G2032R mutation is implicated in tumor growth, as indicated by the investigation of its effects in Ba/F3 cells and the context of progression on crizotinib treatment, suggesting its role in tumor development.

Gene→Variant (gene-first): 6098:G2032R

Genes: 6098

Variants: G2032R

[Paragraph-level] PMCID: PMC10283448 Section: RESULTS PassageIndex: 9

Evidence Type(s): Predictive

Justification: Predictive: The passage indicates that repotrectinib is effective against crizotinib-resistant ROS1 G2032R, suggesting a correlation between the variant and response to therapy.

Gene→Variant (gene-first): 6098:G2032R

Genes: 6098

Variants: G2032R

[Paragraph-level] PMCID: PMC10283448 Section: ABSTRACT PassageIndex: 2

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the high prevalence of the crizotinib-resistant ROS1-G2032R mutation and its implications for treatment response, indicating a correlation with resistance to therapy. Oncogenic: The mention of the ROS1-G2032R mutation in the context of crizotinib resistance suggests that it contributes to tumor progression, which aligns with the definition of an oncogenic variant.

Gene→Variant (gene-first): 6098:G2032R

Genes: 6098

Variants: G2032R