[Paper-level Aggregated] PMCID: PMC10524391

Evidence Type(s): Oncogenic

Summary: Mutation: T790M | Summary: The T790M mutation is associated with tumor development and progression, contributing to resistance in EGFR-mutant lung cancers and recognized as an oncogenic variant in the context of acquired resistance to EGFR-targeted therapies.

Evidence Type: Oncogenic Mutation: L858R | Summary: The L858R mutation is implicated in tumor development, as it is present in tumors alongside other mutations.

Evidence Type: Oncogenic Mutation: L747S | Summary: The L747S mutation is associated with tumor development, as it is found in a tumor with concurrent mutations.

Evidence Type: Oncogenic Mutation: C797S | Summary: The C797S mutation contributes to tumor development or progression as a resistance mutation in EGFR, particularly in the context of EGFR-mutant lung cancers.

Evidence Type: Oncogenic Mutation: V804M | Summary: The RET V804M mutation is linked to tumor development, supporting its classification as an oncogenic variant.

Evidence Type: Oncogenic Mutation: V804E | Summary: The RET V804E mutation is associated with tumor development, indicating its role as an oncogenic driver.

Evidence Type: Oncogenic Mutation: G810S | Summary: The RET G810S mutation is associated with tumor progression, reinforcing its role as an oncogenic driver in RET fusion-positive lung cancers.

Evidence Type: Oncogenic Mutation: G12S | Summary: The KRAS G12S mutation is associated with tumor development or progression, recognized for its contribution to tumor development as part of off-target resistance mechanisms.

Evidence Type: Oncogenic Mutation: V600E | Summary: The BRAF V600E mutation is identified as a hotspot mutation contributing to tumor development or progression, recognized for its role in tumor progression as part of off-target resistance mechanisms.

Gene→Variant (gene-first): EGFR(1956):T790M EGFR(1956):L858R EGFR(1956):L747S EGFR(1956):C797S RET(5979):V804M RET(5979):V804E RET(5979):G810S KRAS(3845):G12S BRAF(673):V600E

Genes: EGFR(1956) RET(5979) KRAS(3845) BRAF(673)

Variants: T790M L858R L747S C797S V804M V804E G810S G12S V600E

[Paper-level Aggregated] PMCID: PMC10524391

Evidence Type(s): Predictive

Summary: Mutation: T790M | Summary: The EGFR T790M mutation is associated with resistance to earlier generation EGFR TKIs and therapeutic EGFR engagement, indicating its predictive role in therapy response when patients are treated with osimertinib.

Evidence Type: Predictive Mutation: C797S | Summary: The C797S mutation is associated with resistance mechanisms and therapeutic EGFR engagement, indicating its potential role in treatment response, including resistance to osimertinib.

Gene→Variant (gene-first): EGFR(1956):T790M EGFR(1956):C797S

Genes: EGFR(1956)

Variants: T790M C797S

[Paragraph-level] PMCID: PMC10524391 Section: ABSTRACT PassageIndex: 6

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: C797S | Summary: The C797S mutation is associated with resistance to osimertinib, indicating its predictive value in therapy response. Evidence Type: Oncogenic | Mutation: C797S | Summary: The C797S mutation contributes to tumor progression in the context of EGFR-mutant lung cancers. Evidence Type: Oncogenic | Mutation: G12S | Summary: The G12S mutation is implicated in tumor development as part of off-target resistance mechanisms. Evidence Type: Oncogenic | Mutation: G810S | Summary: The G810S mutation is associated with tumor progression in RET fusion-positive lung cancers. Evidence Type: Oncogenic | Mutation: T790M | Summary: The T790M mutation is known to contribute to tumor development and resistance in EGFR-mutant lung cancers. Evidence Type: Oncogenic | Mutation: V600E | Summary: The V600E mutation is recognized for its role in tumor progression as part of off-target resistance mechanisms.

Gene→Variant (gene-first): 1956:C797S 3845:G12S 5979:G810S 1956:T790M 673:V600E

Genes: 1956 3845 5979 673

Variants: C797S G12S G810S T790M V600E

[Paragraph-level] PMCID: PMC10524391 Section: RESULTS PassageIndex: 26

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: C797S | Summary: The EGFR C797S mutation is associated with resistance mechanisms, indicating its potential role in treatment response. Evidence Type: Oncogenic | Mutation: V600E | Summary: The BRAF V600E mutation is implicated in tumor development and progression, contributing to oncogenic processes. Evidence Type: Oncogenic | Mutation: V804E | Summary: The RET V804E mutation is associated with tumor development, indicating its role as an oncogenic driver. Evidence Type: Oncogenic | Mutation: V804M | Summary: The RET V804M mutation is also linked to tumor development, supporting its classification as an oncogenic variant. Evidence Type: Oncogenic | Mutation: G12S | Summary: The KRAS G12S mutation is recognized for its contribution to tumor development, marking it as an oncogenic variant. Evidence Type: Oncogenic | Mutation: G810S | Summary: The RET G810S mutation is associated with tumor progression, reinforcing its role as an oncogenic driver.

Gene→Variant (gene-first): 1956:C797S 3845:G12S 5979:G810S 673:V600E 5979:V804E 5979:V804M

Genes: 1956 3845 5979 673

Variants: C797S G12S G810S V600E V804E V804M

[Paragraph-level] PMCID: PMC10524391 Section: RESULTS PassageIndex: 25

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: G12S | Summary: The KRAS G12S mutation is associated with tumor development or progression as it is mentioned in the context of off-target resistance involving receptor tyrosine kinase or MAPK pathway activation. Evidence Type: Oncogenic | Mutation: V600E | Summary: The BRAF V600E mutation is identified as a hotspot mutation contributing to tumor development or progression, as indicated by its presence in cases of off-target resistance.

Gene→Variant (gene-first): 3845:G12S 673:V600E

Genes: 3845 673

Variants: G12S V600E

[Paragraph-level] PMCID: PMC10524391 Section: RESULTS PassageIndex: 24

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: G810S | Summary: The acquired RET G810S mutation is noted in the context of tumor progression, suggesting its contribution to tumor development or progression.

Gene→Variant (gene-first): 5979:G810S

Genes: 5979

Variants: G810S

[Paragraph-level] PMCID: PMC10524391 Section: RESULTS PassageIndex: 23

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: C797S | Summary: The C797S mutation is associated with resistance to therapeutic EGFR engagement, indicating its role in treatment response. Evidence Type: Predictive | Mutation: T790M | Summary: The T790M mutation is implicated in resistance to therapeutic EGFR engagement, suggesting its relevance in treatment response. Evidence Type: Oncogenic | Mutation: C797S | Summary: The C797S mutation contributes to tumor development or progression as a resistance mutation in EGFR. Evidence Type: Oncogenic | Mutation: T790M | Summary: The T790M mutation is a resistance mutation that contributes to tumor development or progression in EGFR. Evidence Type: Oncogenic | Mutation: V804M/E | Summary: The V804M/E mutations are identified as gatekeeper mutations that contribute to tumor development or progression in RET. Evidence Type: Oncogenic | Mutation: G810S | Summary: The G810S mutation is a solvent front mutation that contributes to tumor development or progression in RET.

Gene→Variant (gene-first): 1956:C797S 5979:G810S 1956:T790M 5979:V804M/E

Genes: 1956 5979

Variants: C797S G810S T790M V804M/E

[Paragraph-level] PMCID: PMC10524391 Section: RESULTS PassageIndex: 9

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: T790M | Summary: The EGFR T790M mutation is associated with resistance to earlier generation EGFR TKIs, indicating its predictive role in therapy response when patients are treated with osimertinib. Evidence Type: Oncogenic | Mutation: T790M | Summary: The EGFR T790M mutation contributes to tumor progression and is recognized as an oncogenic variant in the context of acquired resistance to EGFR-targeted therapies.

Gene→Variant (gene-first): 1956:T790M

Genes: 1956

Variants: T790M

[Paragraph-level] PMCID: PMC10524391 Section: RESULTS PassageIndex: 8

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: T790M | Summary: The T790M mutation is associated with tumor development and progression, as it is found in a significant proportion of tumors alongside other mutations. Evidence Type: Oncogenic | Mutation: L858R | Summary: The L858R mutation is implicated in tumor development, as it is present in tumors alongside other mutations. Evidence Type: Oncogenic | Mutation: L747S | Summary: The L747S mutation is associated with tumor development, as it is found in a tumor with concurrent mutations.

Gene→Variant (gene-first): 1956:L747S 1956:L858R 1956:T790M

Genes: 1956

Variants: L747S L858R T790M

[Paper-level Aggregated] PMCID: PMC10524391

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

Justification: Oncogenic: The presence of mutations such as EGFR T790M, L858R, and RET G810S is associated with resistance to targeted therapies, indicating their role in tumor progression and oncogenic potential. Predictive: The identification of specific mutations like EGFR T790M and RET G810S can predict resistance to therapies such as osimertinib, guiding treatment decisions. Functional: The text discusses resistance mutations that affect the function of EGFR and RET kinases, indicating their functional impact on therapeutic engagement and resistance mechanisms. Prognostic: The presence of mutations such as BRAF V600E and KRAS G12S, along with the response rates to treatment, suggests that these mutations may have prognostic implications for patient outcomes.

Gene→Variant (gene-first): EGFR(1956):C797S KRAS(3845):G12S RET(5979):G810S EGFR(1956):T790M BRAF(673):V600E RET(5979):V804E RET(5979):V804M RET(5979):V804M/E EGFR(1956):L747S EGFR(1956):L858R

Genes: EGFR(1956) KRAS(3845) RET(5979) BRAF(673)

Variants: C797S G12S G810S T790M V600E V804E V804M V804M/E L747S L858R

[Paragraph-level] PMCID: PMC10524391 Section: ABSTRACT PassageIndex: 6

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the response rate and disease control rate of patients treated with osimertinib and selpercatinib, indicating that the variants mentioned (C797S, G12S, G810S, V600E) are associated with treatment response and resistance mechanisms. Oncogenic: The variants C797S, G12S, G810S, and V600E are described in the context of resistance mechanisms, suggesting their role in tumor development or progression in the setting of lung cancers.

Gene→Variant (gene-first): 1956:C797S 3845:G12S 5979:G810S 1956:T790M 673:V600E

Genes: 1956 3845 5979 673

Variants: C797S G12S G810S T790M V600E

[Paragraph-level] PMCID: PMC10524391 Section: RESULTS PassageIndex: 26

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses resistance mechanisms related to specific variants, indicating their correlation with treatment response, particularly in the context of on-target and off-target resistance. Oncogenic: The variants mentioned are associated with resistance mechanisms that contribute to tumor development or progression, as they are involved in co-occurring resistance mechanisms in cancer cases.

Gene→Variant (gene-first): 1956:C797S 3845:G12S 5979:G810S 673:V600E 5979:V804E 5979:V804M

Genes: 1956 3845 5979 673

Variants: C797S G12S G810S V600E V804E V804M

[Paragraph-level] PMCID: PMC10524391 Section: RESULTS PassageIndex: 25

Evidence Type(s): Oncogenic

Justification: Oncogenic: The passage discusses hotspot mutations BRAF V600E and KRAS G12S being found in cases of off-target resistance, indicating that these somatic variants contribute to tumor development or progression.

Gene→Variant (gene-first): 3845:G12S 673:V600E

Genes: 3845 673

Variants: G12S V600E

[Paragraph-level] PMCID: PMC10524391 Section: RESULTS PassageIndex: 24

Evidence Type(s): Oncogenic

Justification: Oncogenic: The passage discusses an acquired RET G810S mutation in the context of tumor progression, indicating that this somatic variant may contribute to tumor development or progression.

Gene→Variant (gene-first): 5979:G810S

Genes: 5979

Variants: G810S

[Paragraph-level] PMCID: PMC10524391 Section: RESULTS PassageIndex: 23

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses resistance mutations that affect the engagement of therapeutic EGFR or RET kinases, indicating a correlation with resistance to specific therapies. Oncogenic: The variants mentioned (C797S, T790M, V804M/E, G810S) are described as resistance mutations that contribute to tumor progression by impacting kinase engagement, suggesting their role in oncogenesis.

Gene→Variant (gene-first): 1956:C797S 5979:G810S 1956:T790M 5979:V804M/E

Genes: 1956 5979

Variants: C797S G810S T790M V804M/E

[Paragraph-level] PMCID: PMC10524391 Section: RESULTS PassageIndex: 9

Evidence Type(s): Predictive, Diagnostic

Justification: Predictive: The passage discusses the presence of the EGFR T790M mutation in patients who had received prior EGFR-directed therapy, indicating a correlation with treatment response or resistance to osimertinib. Diagnostic: The mention of the EGFR T790M mutation being detectable at the time of study enrollment suggests its role in classifying or confirming the disease status in patients undergoing treatment.

Gene→Variant (gene-first): 1956:T790M

Genes: 1956

Variants: T790M

[Paragraph-level] PMCID: PMC10524391 Section: RESULTS PassageIndex: 8

Evidence Type(s): Oncogenic, Diagnostic

Justification: Oncogenic: The passage indicates that the variants L747S, L858R, and T790M are present in tumors, suggesting their role in tumor development or progression. Diagnostic: The presence of specific EGFR mutations, including L747S, L858R, and T790M, is used to classify the tumors, indicating their association with the disease.

Gene→Variant (gene-first): 1956:L747S 1956:L858R 1956:T790M

Genes: 1956

Variants: L747S L858R T790M