[Paper-level Aggregated] PMCID: PMC5652823

Evidence Type(s): Oncogenic, Predictive, Functional

Justification: Oncogenic: The text describes multiple mutations, including EGFR-T790M and BRAF V600E, as driver mutations associated with lung cancer, indicating their role in tumorigenesis. Predictive: The presence of the T790M mutation is linked to resistance to first and second-generation EGFR-TKIs and indicates a response to the third-generation EGFR-TKI osimertinib, suggesting its predictive value for treatment outcomes. Functional: The text mentions that the c.2527G>A; p.V843I mutation is biologically activating, indicating its functional role in the context of lung cancer, despite not conferring sensitivity to EGFR-TKIs.

Gene→Variant (gene-first): EGFR(1956):E709A EGFR(1956):G719S EGFR(1956):G719C EGFR(1956):T790M BRAF(673):V600E EGFR(1956):c.2155G>T EGFR(1956):p.G719C TP53(7157):p.R248W EGFR(1956):c.2203G>A EGFR(1956):p.G735S EGFR(1956):c.2258T>C EGFR(1956):p.P753L EGFR(1956):c.2527G>A EGFR(1956):p.V843I EGFR(1956):c.2543C>T EGFR(1956):p.P848L

Genes: EGFR(1956) BRAF(673) TP53(7157)

Variants: E709A G719S G719C T790M V600E c.2155G>T p.G719C p.R248W c.2203G>A p.G735S c.2258T>C p.P753L c.2527G>A p.V843I c.2543C>T p.P848L

[Paragraph-level] PMCID: PMC5652823 Section: RESULTS PassageIndex: 25

Evidence Type(s): Predictive, Prognostic

Justification: Predictive: The passage discusses the response of patients with a T790M mutation to osimertinib treatment, indicating a correlation between the variant and treatment response. Prognostic: The passage mentions progression-free survival (PFS) and overall survival (OS) in relation to the T790M mutation, suggesting a correlation with disease outcome independent of therapy.

Gene→Variant (gene-first): 1956:T790M

Genes: 1956

Variants: T790M

[Paragraph-level] PMCID: PMC5652823 Section: RESULTS PassageIndex: 24

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

Justification: Predictive: The passage discusses the T790M mutation in the context of resistance to EGFR-TKI therapy and its correlation with treatment response, particularly with osimertinib. Diagnostic: The T790M mutation is mentioned as a resistance mutation detected in patients with acquired resistance to EGFR-TKI therapy, indicating its role in classifying the disease state. Oncogenic: The T790M mutation is described as a resistance mutation that contributes to tumor progression in patients undergoing treatment, indicating its role in cancer development. Functional: The passage implies that the T790M mutation alters the response to therapy, suggesting a change in molecular function related to drug resistance mechanisms.

Gene→Variant (gene-first): 1956:G719C 1956:T790M 673:V600E 1956:c.2155G>T 1956:p.G719C 7157:p.R248W

Genes: 1956 673 7157

Variants: G719C T790M V600E c.2155G>T p.G719C p.R248W

[Paragraph-level] PMCID: PMC5652823 Section: RESULTS PassageIndex: 17

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses patients with sensitizing driver mutations receiving targeted therapy, indicating a correlation between the presence of these mutations (including E709A and G719S) and the response to treatment. Oncogenic: The mention of E709A and G719S as part of a complex EGFR mutation suggests that these somatic variants contribute to tumor development or progression, particularly in the context of the patient's advanced disease stage.

Gene→Variant (gene-first): 1956:E709A 1956:G719S

Genes: 1956

Variants: E709A G719S

[Paragraph-level] PMCID: PMC5652823 Section: RESULTS PassageIndex: 13

Evidence Type(s): Oncogenic

Justification: Oncogenic: The passage indicates that the classic V600E mutation was detected in patients, suggesting its role in tumor development or progression, particularly in the context of BRAF mutations.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC5652823 Section: RESULTS PassageIndex: 11

Evidence Type(s): Diagnostic, Predictive, Oncogenic

Justification: Diagnostic: The variant c.2527G>A; p.V843I is associated with lung cancer, as indicated by its reporting in the COSMIC databank and its presence in a patient with NSCLC. Predictive: The passage states that the mutation does not confer sensitivity to EGFR-TKIs, indicating a lack of response to this specific therapy. Oncogenic: The variant is described as "activating from a biological point of view," suggesting it contributes to tumor development or progression in lung cancer.

Gene→Variant (gene-first): 1956:c.2527G>A 1956:p.V843I

Genes: 1956

Variants: c.2527G>A p.V843I

[Paragraph-level] PMCID: PMC5652823 Section: RESULTS PassageIndex: 10

Evidence Type(s): Predictive, Diagnostic, Oncogenic

Justification: Predictive: The passage indicates that the patient showed stable disease on erlotinib, suggesting a correlation between the variant and response to therapy. Diagnostic: The variant is mentioned in the context of being previously described in lung samples, indicating its association with a specific disease subtype (lung cancer). Oncogenic: The variant is discussed in relation to a patient with stage IV lung cancer, suggesting its potential role in tumor development or progression.

Gene→Variant (gene-first): 1956:c.2543C>T 1956:p.P848L

Genes: 1956

Variants: c.2543C>T p.P848L

[Paragraph-level] PMCID: PMC5652823 Section: RESULTS PassageIndex: 9

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the patient's treatment with erlotinib and mentions early progression after disease stabilization, indicating a correlation between the variant and treatment response. Oncogenic: The variant is associated with a patient who has stage IIIA SCC, suggesting that it may contribute to tumor development or progression in the context of lung cancer.

Gene→Variant (gene-first): 1956:c.2258T>C 1956:p.P753L

Genes: 1956

Variants: c.2258T>C p.P753L

[Paragraph-level] PMCID: PMC5652823 Section: RESULTS PassageIndex: 8

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the patient's progressive disease on 2nd line EGFR-TKI therapy with gefitinib, indicating a lack of response to the treatment associated with the variant. Oncogenic: The variant c.2203G>A; p.G735S is mentioned in the context of lung cancer, suggesting it may contribute to tumor development or progression.

Gene→Variant (gene-first): 1956:c.2203G>A 1956:p.G735S

Genes: 1956

Variants: c.2203G>A p.G735S

[Paragraph-level] PMCID: PMC5652823 Section: RESULTS PassageIndex: 6

Evidence Type(s): Oncogenic

Justification: Oncogenic: The passage indicates that the BRAF mutation V600E is classified as an oncogenic driver mutation, suggesting its role in tumor development or progression.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC5652823 Section: ABSTRACT PassageIndex: 7

Evidence Type(s): Predictive, Diagnostic

Justification: Predictive: The passage indicates that patients with the EGFR-T790M mutation responded to the 3rd-generation EGFR-TKI osimertinib, suggesting a correlation between the variant and treatment response. Diagnostic: The EGFR-T790M mutation is mentioned as being revealed in re-biopsies at progression, indicating its role in defining or confirming the presence of a specific disease state in patients treated with EGFR-TKIs.

Gene→Variant (gene-first): 1956:T790M

Genes: 1956

Variants: T790M

[Paragraph-level] PMCID: PMC5652823 Section: ABSTRACT PassageIndex: 7

Evidence Type(s): Predictive, Diagnostic

Justification: Predictive: The passage indicates that patients with the EGFR-T790M mutation responded to the 3rd-generation EGFR-TKI osimertinib, suggesting a correlation between the variant and treatment response. Diagnostic: The EGFR-T790M mutation is mentioned as being revealed in re-biopsies at progression, indicating its role in defining or confirming the presence of a specific disease state in patients treated with EGFR-TKIs.

Gene→Variant (gene-first): 1956:T790M

Genes: 1956

Variants: T790M