41 Matching Annotations
  1. Mar 2026
  2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    Untitled document
    16
    1. karimkhoury04 25 Mar 2026
      EGFR-D770>GY and Other Rare EGFR Exon 20 Insertion Mutations with a G770 Equivalence Are Sensitive to Dacomitinib or Afatinib and Responsive to EGFR Exon 20 Insertion Mutant-Active Inhibitors in Preclinical Models and

      [Paper-level Aggregated] PMCID: PMC8700411

      Evidence Type(s): Functional

      Summary: Mutation: G770 | Summary: The G770 mutation alters molecular or biochemical function as it is associated with changes in the EGFR protein due to the insertion mutations. The preclinical characterization of an EGFR Exon 20 Insertion Mutant with a G770 equivalence indicates that this variant alters molecular or biochemical function.

      Evidence Type: Functional Mutation: V769dupASV | Summary: The V769dupASV mutation affects the biochemical function of EGFR, as evidenced by the differential inhibition of phosphorylated EGFR in response to dacomitinib. Additionally, this mutation shows sensitivity to mobocertinib and poziotinib, suggesting functional alterations in response to these therapies.

      Evidence Type: Functional Mutation: Y764insFQEA | Summary: The Y764insFQEA mutation is described as pan-sensitive to all EGFR TKIs tested, indicating a functional alteration in response to these therapies.

      Gene→Variant (gene-first): EGFR(1956):G770 EGFR(1956):V769dupASV EGFR(1956):Y764insFQEA

      Genes: EGFR(1956)

      Variants: G770 V769dupASV Y764insFQEA

      CIViC paper-level aggregated PMC8700411 Functional
    2. karimkhoury04 25 Mar 2026
      EGFR-D770>GY and Other Rare EGFR Exon 20 Insertion Mutations with a G770 Equivalence Are Sensitive to Dacomitinib or Afatinib and Responsive to EGFR Exon 20 Insertion Mutant-Active Inhibitors in Preclinical Models and

      [Paper-level Aggregated] PMCID: PMC8700411

      Evidence Type(s): Oncogenic

      Summary: Mutation: G770 | Summary: The G770 mutation is part of the EGFR exon 20 insertion mutations, which are known to contribute to tumor development or progression in advanced lung cancers. It is implicated in tumor development and is associated with a lack of response to certain EGFR TKIs, supporting its classification as oncogenic.

      Evidence Type: Oncogenic Mutation: V769dupASV | Summary: The V769dupASV mutation is implicated in driving proliferation in Ba/F3 cells, suggesting its role in tumor development or progression.

      Gene→Variant (gene-first): EGFR(1956):G770 EGFR(1956):V769dupASV

      Genes: EGFR(1956)

      Variants: G770 V769dupASV

      CIViC paper-level aggregated PMC8700411 Oncogenic
    3. karimkhoury04 25 Mar 2026
      EGFR-D770>GY and Other Rare EGFR Exon 20 Insertion Mutations with a G770 Equivalence Are Sensitive to Dacomitinib or Afatinib and Responsive to EGFR Exon 20 Insertion Mutant-Active Inhibitors in Preclinical Models and

      [Paper-level Aggregated] PMCID: PMC8700411

      Evidence Type(s): Diagnostic

      Summary: Mutation: G770 | Summary: The G770 mutation is associated with advanced lung cancers and is used to classify or define a specific subtype of lung cancer related to EGFR Exon 20 insertion mutations.

      Gene→Variant (gene-first): EGFR(1956):G770

      Genes: EGFR(1956)

      Variants: G770

      CIViC paper-level aggregated PMC8700411 Diagnostic
    4. karimkhoury04 25 Mar 2026
      EGFR-D770>GY and Other Rare EGFR Exon 20 Insertion Mutations with a G770 Equivalence Are Sensitive to Dacomitinib or Afatinib and Responsive to EGFR Exon 20 Insertion Mutant-Active Inhibitors in Preclinical Models and

      [Paper-level Aggregated] PMCID: PMC8700411

      Evidence Type(s): Predictive

      Summary: Mutation: D770_N771insSVD | Summary: The D770_N771insSVD mutation is associated with sensitivity to mobocertinib and poziotinib, indicating its predictive value for response to these therapies.

      Evidence Type: Predictive Mutation: V769dupASV | Summary: The V769dupASV mutation shows sensitivity to mobocertinib and poziotinib, but is also associated with a higher IC50 for afatinib and dacomitinib, indicating a correlation with resistance to these therapies. Additionally, it shows altered sensitivity to dacomitinib, suggesting implications for treatment response.

      Evidence Type: Predictive Mutation: G770 | Summary: The G770 mutation is associated with sensitivity to EGFR TKIs such as dacomitinib, afatinib, and mobocertinib, as well as with a lack of response to certain EGFR TKIs. It is also correlated with radiographic responses to therapies like poziotinib and mobocertinib, indicating its predictive value for treatment outcomes in patients with advanced lung cancers.

      Evidence Type: Predictive Mutation: D770 | Summary: The EGFR-D770 mutation is associated with sensitivity to specific 2nd generation EGFR-TKIs, such as afatinib and dacomitinib, indicating its predictive value for therapy response.

      Evidence Type: Predictive Mutation: Y764insFQEA | Summary: The EGFR-Y764insFQEA insertion mutation is responsive to approved EGFR TKIs, highlighting its predictive significance for treatment outcomes.

      Gene→Variant (gene-first): EGFR(1956):D770_N771insSVD EGFR(1956):V769dupASV EGFR(1956):G770 EGFR(1956):D770 EGFR(1956):Y764insFQEA

      Genes: EGFR(1956)

      Variants: D770_N771insSVD V769dupASV G770 D770 Y764insFQEA

      CIViC paper-level aggregated PMC8700411 Predictive
    5. karimkhoury04 25 Mar 2026
      Epidermal growth factor receptor (EGFR) exon 20 insertion mutations account for a tenth of all EGFR mutations in lung cancers. An important unmet clinical need is the identification of EGFR exon 20 insertion mutants that

      [Paragraph-level] PMCID: PMC8700411 Section: ABSTRACT PassageIndex: 1

      Evidence Type(s): Predictive

      Summary: Evidence Type: Predictive | Mutation: D770 | Summary: The EGFR-D770 mutation is associated with sensitivity to specific 2nd generation EGFR-TKIs, such as afatinib and dacomitinib, indicating its predictive value for therapy response. Evidence Type: Predictive | Mutation: G770 | Summary: The EGFR-G770 mutation shows sensitivity to approved 2nd generation EGFR TKIs and EGFR exon 20 insertion mutant-active TKIs, suggesting its predictive role in therapy response. Evidence Type: Predictive | Mutation: Y764insFQEA | Summary: The EGFR-Y764insFQEA insertion mutation is responsive to approved EGFR TKIs, highlighting its predictive significance for treatment outcomes.

      Gene→Variant (gene-first): 1956:D770 1956:G770 1956:Y764insFQEA

      Genes: 1956

      Variants: D770 G770 Y764insFQEA

      CIViC paragraph-level PMC8700411 Predictive
    6. karimkhoury04 25 Mar 2026
      Although these cases are limited in number and by reporting biases, they provide supporting evidence that EGFR-D770>GY and other exon 20 insertion mutations with G770 equivalence are sensitive to the clinically available

      [Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 13

      Evidence Type(s): Predictive, Oncogenic

      Summary: Evidence Type: Predictive | Mutation: G770 | Summary: The variant G770 is associated with sensitivity to EGFR TKIs such as dacomitinib, afatinib, and mobocertinib, indicating its predictive value for therapy response. Evidence Type: Oncogenic | Mutation: G770 | Summary: The G770 variant is implicated in tumor development or progression, as it is part of exon 20 insertion mutations in EGFR.

      Gene→Variant (gene-first): 1956:G770

      Genes: 1956

      Variants: G770

      CIViC paragraph-level PMC8700411 Predictive Oncogenic
    7. karimkhoury04 25 Mar 2026
      The majority:but not all:of cases that received poziotinib or mobocertinib in this compiled cohort of advanced lung cancers harboring EGFR exon 20 insertion mutations with G770 equivalence had radiographic responses (Tab

      [Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 12

      Evidence Type(s): Predictive, Oncogenic

      Summary: Evidence Type: Predictive | Mutation: G770 | Summary: The G770 mutation is associated with radiographic responses to the therapies poziotinib and mobocertinib in advanced lung cancers, indicating its predictive value for treatment response. Evidence Type: Oncogenic | Mutation: G770 | Summary: The G770 mutation is part of EGFR exon 20 insertion mutations that contribute to tumor development in advanced lung cancers, supporting its classification as oncogenic.

      Gene→Variant (gene-first): 1956:G770

      Genes: 1956

      Variants: G770

      CIViC paragraph-level PMC8700411 Predictive Oncogenic
    8. karimkhoury04 25 Mar 2026
      We identified seven reports from the literature and added one case from our institutional cohort that detailed partial clinical-radiographic parameters in patients with metastatic lung cancers harboring EGFR exon 20 inse

      [Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 10

      Evidence Type(s): Predictive, Oncogenic

      Summary: Evidence Type: Predictive | Mutation: G770 | Summary: The G770 mutation is associated with a lack of response to certain EGFR TKIs, indicating its predictive value regarding therapy resistance. Evidence Type: Oncogenic | Mutation: G770 | Summary: The G770 mutation is part of EGFR exon 20 insertion mutations that contribute to tumor development in patients with metastatic lung cancers.

      Gene→Variant (gene-first): 1956:G770

      Genes: 1956

      Variants: G770

      CIViC paragraph-level PMC8700411 Predictive Oncogenic
    9. karimkhoury04 25 Mar 2026
      3.3. Clinical Outcomes of Reported Patients with Advanced Lung Cancers Harboring EGFR Exon 20 Insertion Mutations Encompassing G770 Equivalence

      [Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 9

      Evidence Type(s): Oncogenic, Diagnostic

      Summary: Evidence Type: Oncogenic | Mutation: G770 | Summary: The passage discusses advanced lung cancers harboring EGFR Exon 20 insertion mutations, indicating that the G770 mutation contributes to tumor development or progression. Evidence Type: Diagnostic | Mutation: G770 | Summary: The mention of advanced lung cancers associated with EGFR Exon 20 insertion mutations suggests that the G770 mutation is used to classify or define a specific subtype of lung cancer.

      Gene→Variant (gene-first): 1956:G770

      Genes: 1956

      Variants: G770

      CIViC paragraph-level PMC8700411 Oncogenic Diagnostic
    10. karimkhoury04 25 Mar 2026
      Our aforementioned preclinical results confirmed the structural modeling of EGFR-D770>GY (Figure 1A) and led us to speculate that patients with advanced lung cancers harboring EGFR exon 20 insertion mutations with a G770

      [Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 8

      Evidence Type(s): Predictive

      Summary: Evidence Type: Predictive | Mutation: G770 | Summary: The G770 mutation in EGFR is speculated to correlate with response to specific therapies such as afatinib, dacomitinib, poziotinib, and mobocertinib, indicating its predictive value for treatment outcomes in patients with advanced lung cancers.

      Gene→Variant (gene-first): 1956:G770

      Genes: 1956

      Variants: G770

      CIViC paragraph-level PMC8700411 Predictive
    11. karimkhoury04 25 Mar 2026
      The exquisite sensitivity to 2nd generation EGFR TKIs was confirmed at the biochemical level. In Western blot experiments, the phosphorylated form of EGFR was readily inhibited by 10 nM and higher doses of dacomitinib in

      [Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 7

      Evidence Type(s): Predictive, Functional

      Summary: Evidence Type: Predictive | Mutation: V769dupASV | Summary: The V769dupASV mutation shows altered sensitivity to dacomitinib, indicating a correlation with response to therapy. Evidence Type: Functional | Mutation: V769dupASV | Summary: The V769dupASV mutation affects the biochemical function of EGFR, as evidenced by the differential inhibition of phosphorylated EGFR in response to dacomitinib.

      Gene→Variant (gene-first): 1956:V769dupASV

      Genes: 1956

      Variants: V769dupASV

      CIViC paragraph-level PMC8700411 Predictive Functional
    12. karimkhoury04 25 Mar 2026
      To highlight the differences in proliferation assays between Ba/F3 cells driven by the EGFR-D770>GY mutant and the more typical EGFR-A767_V769dupASV mutant, we show the dose-response curve for increasing concentrations o

      [Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 6

      Evidence Type(s): Predictive, Oncogenic

      Summary: Evidence Type: Predictive | Mutation: V769dupASV | Summary: The V769dupASV mutation is associated with a higher IC50 for afatinib and dacomitinib, indicating a correlation with resistance to these therapies. Evidence Type: Oncogenic | Mutation: V769dupASV | Summary: The V769dupASV mutation is implicated in driving proliferation in Ba/F3 cells, suggesting its role in tumor development or progression.

      Gene→Variant (gene-first): 1956:V769dupASV

      Genes: 1956

      Variants: V769dupASV

      CIViC paragraph-level PMC8700411 Predictive Oncogenic
    13. karimkhoury04 25 Mar 2026
      Our group generated a Ba/F3 cell line driven by the EGFR-D770>GY mutant in order to compare its properties with our previously described isogenic Ba/F3 preclinical models of exon 20 insertion mutants (Figure 2). To evalu

      [Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 5

      Evidence Type(s): Predictive, Functional

      Summary: Evidence Type: Predictive | Mutation: D770_N771insSVD | Summary: The D770_N771insSVD mutation is associated with sensitivity to mobocertinib and poziotinib, indicating its predictive value for response to these therapies. Evidence Type: Predictive | Mutation: V769dupASV | Summary: The V769dupASV mutation shows sensitivity to mobocertinib and poziotinib, suggesting it has predictive implications for treatment response. Evidence Type: Functional | Mutation: Y764insFQEA | Summary: The Y764insFQEA mutation is described as pan-sensitive to all EGFR TKIs tested, indicating a functional alteration in response to these therapies.

      Gene→Variant (gene-first): 1956:D770_N771insSVD 1956:V769dupASV 1956:Y764insFQEA

      Genes: 1956

      Variants: D770_N771insSVD V769dupASV Y764insFQEA

      CIViC paragraph-level PMC8700411 Predictive Functional
    14. karimkhoury04 25 Mar 2026
      3.2. Preclinical Characterization of an EGFR Exon 20 Insertion Mutant with a G770 Equivalence

      [Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 4

      Evidence Type(s): Functional

      Summary: Evidence Type: Functional | Mutation: G770 | Summary: The passage discusses the preclinical characterization of an EGFR Exon 20 Insertion Mutant with a G770 equivalence, indicating that this variant alters molecular or biochemical function.

      Gene→Variant (gene-first): 1956:G770

      Genes: 1956

      Variants: G770

      CIViC paragraph-level PMC8700411 Functional
    15. karimkhoury04 25 Mar 2026
      We queried three separate cohorts of EGFR exon 20 insertion mutations. Out of the 429 cases reported, 17 (3.96%) had the EGFR mutation leading to G770 equivalent change in the context of an insertion (Figure 1B). The typ

      [Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 3

      Evidence Type(s): Oncogenic, Functional

      Summary: Evidence Type: Oncogenic | Mutation: G770 | Summary: The G770 mutation is part of the EGFR exon 20 insertion mutations, which are known to contribute to tumor development or progression. Evidence Type: Functional | Mutation: G770 | Summary: The G770 mutation alters molecular or biochemical function as it is associated with changes in the EGFR protein due to the insertion mutations.

      Gene→Variant (gene-first): 1956:G770

      Genes: 1956

      Variants: G770

      CIViC paragraph-level PMC8700411 Oncogenic Functional
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    pmc.ncbi.nlm.nih.gov/articles/PMC8700411/pdf/cells-10-03561.pdf
  3. Feb 2026
  4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    Untitled document
    25
    1. karim2001khoury 19 Feb 2026
      EGFR-D770>GY and Other Rare EGFR Exon 20 Insertion Mutations with a G770 Equivalence Are Sensitive to Dacomitinib or Afatinib and Responsive to EGFR Exon 20 Insertion Mutant-Active Inhibitors in Preclinical Models and

      [Paper-level Aggregated] PMCID: PMC8700411

      Evidence Type(s): Oncogenic, Predictive, Prognostic

      Justification: Oncogenic: The text describes EGFR exon 20 insertion mutations, including G770 equivalence, as being associated with sensitivity to specific EGFR TKIs, indicating their role in driving cancer progression. Predictive: The evidence suggests that patients with EGFR exon 20 insertion mutations, particularly those with G770 equivalence, can be predicted to respond to certain EGFR TKIs, such as afatinib and dacomitinib, based on preclinical and clinical data. Prognostic: The clinical outcomes reported for patients with EGFR exon 20 insertion mutations indicate that these mutations can influence treatment responses and outcomes, suggesting a prognostic role in advanced lung cancers.

      Gene→Variant (gene-first): EGFR(1956):D770 EGFR(1956):G770 EGFR(1956):Y764insFQEA EGFR(1956):D770_N771insSVD EGFR(1956):V769dupASV

      Genes: EGFR(1956)

      Variants: D770 G770 Y764insFQEA D770_N771insSVD V769dupASV

      CIViC paper-level aggregated PMC8700411
    2. karim2001khoury 19 Feb 2026
      Epidermal growth factor receptor (EGFR) exon 20 insertion mutations account for a tenth of all EGFR mutations in lung cancers. An important unmet clinical need is the identification of EGFR exon 20 insertion mutants that

      [Paragraph-level] PMCID: PMC8700411 Section: ABSTRACT PassageIndex: 1

      Evidence Type(s): Predictive, Diagnostic, Oncogenic

      Justification: Predictive: The passage discusses the sensitivity of specific EGFR variants (D770 and G770) to various EGFR-TKIs, indicating a correlation with response to therapy. Diagnostic: The mention of EGFR exon 20 insertion mutations and their frequency in lung cancer suggests that these variants are used to classify and define a specific subtype of the disease. Oncogenic: The variants D770 and G770 are described as contributing to tumor development, as they are part of the EGFR mutations associated with lung cancer.

      Gene→Variant (gene-first): 1956:D770 1956:G770 1956:Y764insFQEA

      Genes: 1956

      Variants: D770 G770 Y764insFQEA

      CIViC paragraph-level PMC8700411 Predictive Diagnostic Oncogenic
    3. karim2001khoury 19 Feb 2026
      Although these cases are limited in number and by reporting biases, they provide supporting evidence that EGFR-D770>GY and other exon 20 insertion mutations with G770 equivalence are sensitive to the clinically available

      [Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 13

      Evidence Type(s): Predictive

      Justification: Predictive: The passage indicates that the variant G770 and other exon 20 insertion mutations are sensitive to specific EGFR TKIs, suggesting a correlation with treatment response.

      Gene→Variant (gene-first): 1956:G770

      Genes: 1956

      Variants: G770

      CIViC paragraph-level PMC8700411 Predictive
    4. karim2001khoury 19 Feb 2026
      The majority:but not all:of cases that received poziotinib or mobocertinib in this compiled cohort of advanced lung cancers harboring EGFR exon 20 insertion mutations with G770 equivalence had radiographic responses (Tab

      [Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 12

      Evidence Type(s): Predictive, Diagnostic

      Justification: Predictive: The passage discusses the correlation between the G770 variant and radiographic responses to therapies (poziotinib and mobocertinib) in advanced lung cancers, indicating its predictive nature regarding treatment response. Diagnostic: The mention of "EGFR exon 20 insertion mutations with G770 equivalence" suggests that the G770 variant is used to classify or define a specific subtype of lung cancer, supporting its role as a diagnostic marker.

      Gene→Variant (gene-first): 1956:G770

      Genes: 1956

      Variants: G770

      CIViC paragraph-level PMC8700411 Predictive Diagnostic
    5. karim2001khoury 19 Feb 2026
      We identified seven reports from the literature and added one case from our institutional cohort that detailed partial clinical-radiographic parameters in patients with metastatic lung cancers harboring EGFR exon 20 inse

      [Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 10

      Evidence Type(s): Predictive, Oncogenic

      Justification: Predictive: The passage discusses the response of patients with metastatic lung cancers harboring EGFR exon 20 insertion mutations, including G770, to various EGFR TKIs, indicating a correlation with treatment response. Oncogenic: The mention of tumors harboring EGFR exon 20 insertion mutations, including G770, suggests that this somatic variant contributes to tumor development or progression in the context of metastatic lung cancers.

      Gene→Variant (gene-first): 1956:G770

      Genes: 1956

      Variants: G770

      CIViC paragraph-level PMC8700411 Predictive Oncogenic
    6. karim2001khoury 19 Feb 2026
      3.3. Clinical Outcomes of Reported Patients with Advanced Lung Cancers Harboring EGFR Exon 20 Insertion Mutations Encompassing G770 Equivalence

      [Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 9

      Evidence Type(s): Diagnostic, Oncogenic

      Justification: Diagnostic: The passage discusses patients with advanced lung cancers harboring EGFR Exon 20 insertion mutations, indicating that the variant is used to classify or define a specific disease subtype. Oncogenic: The mention of advanced lung cancers suggests that the G770 variant contributes to tumor development or progression, aligning with the definition of an oncogenic variant.

      Gene→Variant (gene-first): 1956:G770

      Genes: 1956

      Variants: G770

      CIViC paragraph-level PMC8700411 Diagnostic Oncogenic
    7. karim2001khoury 19 Feb 2026
      Our aforementioned preclinical results confirmed the structural modeling of EGFR-D770>GY (Figure 1A) and led us to speculate that patients with advanced lung cancers harboring EGFR exon 20 insertion mutations with a G770

      [Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 8

      Evidence Type(s): Predictive

      Justification: Predictive: The passage discusses the potential response of patients with advanced lung cancers harboring the G770 variant to specific therapies, indicating a correlation with treatment response.

      Gene→Variant (gene-first): 1956:G770

      Genes: 1956

      Variants: G770

      CIViC paragraph-level PMC8700411 Predictive
    8. karim2001khoury 19 Feb 2026
      The exquisite sensitivity to 2nd generation EGFR TKIs was confirmed at the biochemical level. In Western blot experiments, the phosphorylated form of EGFR was readily inhibited by 10 nM and higher doses of dacomitinib in

      [Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 7

      Evidence Type(s): Predictive, Functional

      Justification: Predictive: The passage discusses the sensitivity of the V769dupASV variant to 2nd generation EGFR TKIs, indicating a correlation with response to therapy. Functional: The variant V769dupASV is shown to alter the biochemical function of EGFR, as evidenced by the differing levels of inhibition of phosphorylated EGFR in response to dacomitinib.

      Gene→Variant (gene-first): 1956:V769dupASV

      Genes: 1956

      Variants: V769dupASV

      CIViC paragraph-level PMC8700411 Predictive Functional
    9. karim2001khoury 19 Feb 2026
      To highlight the differences in proliferation assays between Ba/F3 cells driven by the EGFR-D770>GY mutant and the more typical EGFR-A767_V769dupASV mutant, we show the dose-response curve for increasing concentrations o

      [Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 6

      Evidence Type(s): Predictive, Oncogenic

      Justification: Predictive: The passage discusses the response of cells with the A767_V769dupASV mutant to specific therapies (afatinib and dacomitinib), indicating a correlation between the variant and treatment sensitivity. Oncogenic: The variant A767_V769dupASV is mentioned in the context of proliferation assays, suggesting that it contributes to tumor development or progression in the tested cell lines.

      Gene→Variant (gene-first): 1956:V769dupASV

      Genes: 1956

      Variants: V769dupASV

      CIViC paragraph-level PMC8700411 Predictive Oncogenic
    10. karim2001khoury 19 Feb 2026
      Our group generated a Ba/F3 cell line driven by the EGFR-D770>GY mutant in order to compare its properties with our previously described isogenic Ba/F3 preclinical models of exon 20 insertion mutants (Figure 2). To evalu

      [Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 5

      Evidence Type(s): Predictive, Oncogenic

      Justification: Predictive: The passage discusses the sensitivity and resistance of various EGFR mutations, including D770_N771insSVD, V769dupASV, and Y764insFQEA, to different EGFR TKIs, indicating a correlation with response to therapy. Oncogenic: The variants mentioned are associated with the development of cancer, as they are described in the context of a Ba/F3 cell line model driven by specific EGFR mutations, which contribute to tumor behavior.

      Gene→Variant (gene-first): 1956:D770_N771insSVD 1956:V769dupASV 1956:Y764insFQEA

      Genes: 1956

      Variants: D770_N771insSVD V769dupASV Y764insFQEA

      CIViC paragraph-level PMC8700411 Predictive Oncogenic
    12. karim2001khoury 19 Feb 2026
      We queried three separate cohorts of EGFR exon 20 insertion mutations. Out of the 429 cases reported, 17 (3.96%) had the EGFR mutation leading to G770 equivalent change in the context of an insertion (Figure 1B). The typ

      [Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 3

      Evidence Type(s): Diagnostic, Oncogenic

      Justification: Diagnostic: The passage discusses the prevalence of the G770 variant in a cohort of cases with EGFR exon 20 insertion mutations, indicating its association with a specific mutation type and providing context for its classification. Oncogenic: The mention of the G770 variant in the context of EGFR mutations suggests its role in tumor development or progression, as it is part of a known oncogenic pathway associated with cancer.

      Gene→Variant (gene-first): 1956:G770

      Genes: 1956

      Variants: G770

      CIViC paragraph-level PMC8700411 Diagnostic Oncogenic
    13. karim2001khoury 19 Feb 2026
      3.1. Frequency of EGFR Exon 20 Insertions with a G770 Equivalence

      [Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 2

      Evidence Type(s): Diagnostic

      Justification: Diagnostic: The mention of "frequency" in relation to "EGFR Exon 20 Insertions with a G770 Equivalence" suggests that the variant is being used to classify or define a specific disease or subtype.

      Gene→Variant (gene-first): 1956:G770

      Genes: 1956

      Variants: G770

      CIViC paragraph-level PMC8700411 Diagnostic
    14. karim2001khoury 19 Feb 2026
      Epidermal growth factor receptor (EGFR) exon 20 insertion mutations account for a tenth of all EGFR mutations in lung cancers. An important unmet clinical need is the identification of EGFR exon 20 insertion mutants that

      [Paragraph-level] PMCID: PMC8700411 Section: ABSTRACT PassageIndex: 1

      Evidence Type(s): Predictive, Diagnostic, Oncogenic

      Justification: Predictive: The passage discusses the sensitivity of specific EGFR variants (D770 and G770) to various EGFR-TKIs, indicating a correlation with response to therapy. Diagnostic: The mention of EGFR exon 20 insertion mutations and their frequency in lung cancer suggests that these variants are used to classify and define a specific subtype of the disease. Oncogenic: The variants D770 and G770 are described as contributing to tumor development, as they are part of the EGFR mutations associated with lung cancer.

      Gene→Variant (gene-first): 1956:D770 1956:G770 1956:Y764insFQEA

      Genes: 1956

      Variants: D770 G770 Y764insFQEA

      CIViC paragraph-level PMC8700411 Predictive Diagnostic Oncogenic
    15. karim2001khoury 19 Feb 2026
      Although these cases are limited in number and by reporting biases, they provide supporting evidence that EGFR-D770>GY and other exon 20 insertion mutations with G770 equivalence are sensitive to the clinically available

      [Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 13

      Evidence Type(s): Predictive

      Justification: Predictive: The passage indicates that the variant G770 and other exon 20 insertion mutations are sensitive to specific EGFR TKIs, suggesting a correlation with treatment response.

      Gene→Variant (gene-first): 1956:G770

      Genes: 1956

      Variants: G770

      CIViC paragraph-level PMC8700411 Predictive
    16. karim2001khoury 19 Feb 2026
      The majority:but not all:of cases that received poziotinib or mobocertinib in this compiled cohort of advanced lung cancers harboring EGFR exon 20 insertion mutations with G770 equivalence had radiographic responses (Tab

      [Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 12

      Evidence Type(s): Predictive, Diagnostic

      Justification: Predictive: The passage discusses the correlation between the G770 variant and radiographic responses to therapies (poziotinib and mobocertinib) in advanced lung cancers, indicating its predictive nature regarding treatment response. Diagnostic: The mention of "EGFR exon 20 insertion mutations with G770 equivalence" suggests that the G770 variant is used to classify or define a specific subtype of lung cancer, supporting its role as a diagnostic marker.

      Gene→Variant (gene-first): 1956:G770

      Genes: 1956

      Variants: G770

      CIViC paragraph-level PMC8700411 Predictive Diagnostic
    17. karim2001khoury 19 Feb 2026
      We identified seven reports from the literature and added one case from our institutional cohort that detailed partial clinical-radiographic parameters in patients with metastatic lung cancers harboring EGFR exon 20 inse

      [Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 10

      Evidence Type(s): Predictive, Oncogenic

      Justification: Predictive: The passage discusses the response of patients with metastatic lung cancers harboring EGFR exon 20 insertion mutations, including G770, to various EGFR TKIs, indicating a correlation with treatment response. Oncogenic: The mention of tumors harboring EGFR exon 20 insertion mutations, including G770, suggests that this somatic variant contributes to tumor development or progression in the context of metastatic lung cancers.

      Gene→Variant (gene-first): 1956:G770

      Genes: 1956

      Variants: G770

      CIViC paragraph-level PMC8700411 Predictive Oncogenic
    18. karim2001khoury 19 Feb 2026
      3.3. Clinical Outcomes of Reported Patients with Advanced Lung Cancers Harboring EGFR Exon 20 Insertion Mutations Encompassing G770 Equivalence

      [Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 9

      Evidence Type(s): Diagnostic, Oncogenic

      Justification: Diagnostic: The passage discusses patients with advanced lung cancers harboring EGFR Exon 20 insertion mutations, indicating that the variant is used to classify or define a specific disease subtype. Oncogenic: The mention of advanced lung cancers suggests that the G770 variant contributes to tumor development or progression, aligning with the definition of an oncogenic variant.

      Gene→Variant (gene-first): 1956:G770

      Genes: 1956

      Variants: G770

      CIViC paragraph-level PMC8700411 Diagnostic Oncogenic
    19. karim2001khoury 19 Feb 2026
      Our aforementioned preclinical results confirmed the structural modeling of EGFR-D770>GY (Figure 1A) and led us to speculate that patients with advanced lung cancers harboring EGFR exon 20 insertion mutations with a G770

      [Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 8

      Evidence Type(s): Predictive

      Justification: Predictive: The passage discusses the potential response of patients with advanced lung cancers harboring the G770 variant to specific therapies, indicating a correlation with treatment response.

      Gene→Variant (gene-first): 1956:G770

      Genes: 1956

      Variants: G770

      CIViC paragraph-level PMC8700411 Predictive
    20. karim2001khoury 19 Feb 2026
      The exquisite sensitivity to 2nd generation EGFR TKIs was confirmed at the biochemical level. In Western blot experiments, the phosphorylated form of EGFR was readily inhibited by 10 nM and higher doses of dacomitinib in

      [Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 7

      Evidence Type(s): Predictive, Functional

      Justification: Predictive: The passage discusses the sensitivity of the V769dupASV variant to 2nd generation EGFR TKIs, indicating a correlation with response to therapy. Functional: The variant V769dupASV is shown to alter the biochemical function of EGFR, as evidenced by the differing levels of inhibition of phosphorylated EGFR in response to dacomitinib.

      Gene→Variant (gene-first): 1956:V769dupASV

      Genes: 1956

      Variants: V769dupASV

      CIViC paragraph-level PMC8700411 Predictive Functional
    21. karim2001khoury 19 Feb 2026
      To highlight the differences in proliferation assays between Ba/F3 cells driven by the EGFR-D770>GY mutant and the more typical EGFR-A767_V769dupASV mutant, we show the dose-response curve for increasing concentrations o

      [Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 6

      Evidence Type(s): Predictive, Oncogenic

      Justification: Predictive: The passage discusses the response of cells with the A767_V769dupASV mutant to specific therapies (afatinib and dacomitinib), indicating a correlation between the variant and treatment sensitivity. Oncogenic: The variant A767_V769dupASV is mentioned in the context of proliferation assays, suggesting that it contributes to tumor development or progression in the tested cell lines.

      Gene→Variant (gene-first): 1956:V769dupASV

      Genes: 1956

      Variants: V769dupASV

      CIViC paragraph-level PMC8700411 Predictive Oncogenic
    22. karim2001khoury 19 Feb 2026
      Our group generated a Ba/F3 cell line driven by the EGFR-D770>GY mutant in order to compare its properties with our previously described isogenic Ba/F3 preclinical models of exon 20 insertion mutants (Figure 2). To evalu

      [Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 5

      Evidence Type(s): Predictive, Oncogenic

      Justification: Predictive: The passage discusses the sensitivity and resistance of various EGFR mutations, including D770_N771insSVD, V769dupASV, and Y764insFQEA, to different EGFR TKIs, indicating a correlation with response to therapy. Oncogenic: The variants mentioned are associated with the development of cancer, as they are described in the context of a Ba/F3 cell line model driven by specific EGFR mutations, which contribute to tumor behavior.

      Gene→Variant (gene-first): 1956:D770_N771insSVD 1956:V769dupASV 1956:Y764insFQEA

      Genes: 1956

      Variants: D770_N771insSVD V769dupASV Y764insFQEA

      CIViC paragraph-level PMC8700411 Predictive Oncogenic
    24. karim2001khoury 19 Feb 2026
      We queried three separate cohorts of EGFR exon 20 insertion mutations. Out of the 429 cases reported, 17 (3.96%) had the EGFR mutation leading to G770 equivalent change in the context of an insertion (Figure 1B). The typ

      [Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 3

      Evidence Type(s): Diagnostic, Oncogenic

      Justification: Diagnostic: The passage discusses the prevalence of the G770 variant in a cohort of cases with EGFR exon 20 insertion mutations, indicating its association with a specific mutation type and providing context for its classification. Oncogenic: The mention of the G770 variant in the context of EGFR mutations suggests its role in tumor development or progression, as it is part of a known oncogenic pathway associated with cancer.

      Gene→Variant (gene-first): 1956:G770

      Genes: 1956

      Variants: G770

      CIViC paragraph-level PMC8700411 Diagnostic Oncogenic
    25. karim2001khoury 19 Feb 2026
      3.1. Frequency of EGFR Exon 20 Insertions with a G770 Equivalence

      [Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 2

      Evidence Type(s): Diagnostic

      Justification: Diagnostic: The mention of "frequency" in relation to "EGFR Exon 20 Insertions with a G770 Equivalence" suggests that the variant is being used to classify or define a specific disease or subtype.

      Gene→Variant (gene-first): 1956:G770

      Genes: 1956

      Variants: G770

      CIViC paragraph-level PMC8700411 Diagnostic
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    pmc.ncbi.nlm.nih.gov/articles/PMC8700411/pdf/cells-10-03561.pdf