[Paper-level Aggregated] PMCID: PMC1240052

Evidence Type(s): Functional

Summary: Mutation: D837A | Summary: The D837A mutation is described as kinase-dead and kinase-inactive, failing to induce colony formation, indicating an alteration in molecular function compared to the wild-type EGFR.

Evidence Type: Functional Mutation: L858R | Summary: The L858R mutation in EGFR is associated with ligand-independent autophosphorylation, constitutive phosphorylation of Shc, and constitutive activation of STAT signaling pathways, indicating alterations in molecular function related to receptor activation and downstream signaling pathways.

Evidence Type: Functional Mutation: mutant EGFR | Summary: The mutant EGFR leads to constitutive activation of signaling pathways, indicating an alteration in molecular function related to cell survival.

Gene→Variant (gene-first): EGFR(1956):D837A EGFR(1956):L858R NA:mutant EGFR

Genes: EGFR(1956) NA

Variants: D837A L858R mutant EGFR

[Paper-level Aggregated] PMCID: PMC1240052

Evidence Type(s): Oncogenic

Summary: Mutation: G719S | Summary: The G719S mutation contributes to tumor development by transforming NIH-3T3 cells to anchorage independence and promoting tumor formation in immunocompromised mice, indicating its role in altered cellular behavior and tumor progression.

Evidence Type: Oncogenic Mutation: L858R | Summary: The L858R mutation contributes to tumor development and progression by transforming NIH-3T3 cells, enhancing anchorage-independent growth, and activating oncogenic signaling pathways. It has been shown to form tumors in immunocompromised mice and is associated with constitutive activation of downstream signaling pathways.

Evidence Type: Oncogenic Mutation: A750P | Summary: The A750P mutation contributes to tumor development by promoting colony formation in soft agar, indicating its transforming activity.

Evidence Type: Oncogenic Mutation: D770_N771insNPG | Summary: The D770_N771insNPG mutation demonstrates transforming activity, contributing to tumor development as indicated by increased colony formation efficiency in NIH-3T3 cells.

Evidence Type: Oncogenic Mutation: L747_E749del | Summary: The L747_E749del mutation has transforming activity, contributing to tumor development through enhanced colony formation in soft agar.

Evidence Type: Oncogenic Mutation: L747_E749del A750P | Summary: The L747_E749del A750P deletion and insertion mutants formed colonies in soft agar with high efficiency, suggesting their oncogenic potential.

Evidence Type: Oncogenic Mutation: mutant EGFR | Summary: The mutant EGFR contributes to tumor development by activating downstream signaling pathways involved in promoting cell survival.

Gene→Variant (gene-first): EGFR(1956):G719S EGFR(1956):L858R EGFR(1956):A750P EGFR(1956):D770_N771insNPG NA:L747_E749del EGFR(1956):L747_E749del A750P NA:mutant EGFR

Genes: EGFR(1956) NA

Variants: G719S L858R A750P D770_N771insNPG L747_E749del L747_E749del A750P mutant EGFR

[Paper-level Aggregated] PMCID: PMC1240052

Evidence Type(s): Predictive

Summary: Mutation: G719S | Summary: The G719S mutation is associated with resistance to gefitinib, indicating its predictive value for therapy response in lung adenocarcinoma patients.

Evidence Type: Predictive Mutation: L747_E749del A750P | Summary: The L747_E749del A750P mutation correlates with sensitivity to gefitinib and erlotinib, supporting its predictive role in therapy response for lung adenocarcinoma.

Evidence Type: Predictive Mutation: L858R | Summary: The L858R mutation is linked to increased sensitivity to gefitinib and erlotinib, demonstrating its predictive significance for treatment outcomes in lung adenocarcinoma patients. Additionally, it is associated with a response to the irreversible EGFR inhibitor CL-387,785, which shows greater effectiveness compared to gefitinib or erlotinib in inhibiting colony formation and autophosphorylation.

Gene→Variant (gene-first): EGFR(1956):G719S EGFR(1956):L747_E749del A750P EGFR(1956):L858R

Genes: EGFR(1956)

Variants: G719S L747_E749del A750P L858R

[Paragraph-level] PMCID: PMC1240052 Section: RESULTS PassageIndex: 19

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: L858R | Summary: The L858R mutation is associated with a response to the irreversible EGFR inhibitor CL-387,785, which shows greater effectiveness compared to gefitinib or erlotinib in inhibiting colony formation and autophosphorylation. Evidence Type: Oncogenic | Mutation: L858R | Summary: The L858R mutation contributes to tumor development or progression, as indicated by its role in transformation and autophosphorylation in cancer cells.

Gene→Variant (gene-first): 1956:L858R

Genes: 1956

Variants: L858R

[Paragraph-level] PMCID: PMC1240052 Section: RESULTS PassageIndex: 16

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: G719S | Summary: The G719S mutation is associated with resistance to gefitinib, indicating its predictive value for therapy response in lung adenocarcinoma patients. Evidence Type: Predictive | Mutation: L747_E749del A750P | Summary: The L747_E749del A750P mutation correlates with sensitivity to gefitinib and erlotinib, supporting its predictive role in therapy response for lung adenocarcinoma. Evidence Type: Predictive | Mutation: L858R | Summary: The L858R mutation is linked to increased sensitivity to gefitinib and erlotinib, demonstrating its predictive significance for treatment outcomes in lung adenocarcinoma patients.

Gene→Variant (gene-first): 1956:G719S 1956:L747_E749del A750P 1956:L858R

Genes: 1956

Variants: G719S L747_E749del A750P L858R

[Paragraph-level] PMCID: PMC1240052 Section: RESULTS PassageIndex: 14

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: mutant EGFR | Summary: The mutant EGFR leads to constitutive activation of signaling pathways, indicating an alteration in molecular function related to cell survival. Evidence Type: Oncogenic | Mutation: mutant EGFR | Summary: The mutant EGFR contributes to tumor development by activating downstream signaling pathways, which are involved in promoting cell survival.

Gene→Variant (gene-first): 207:serine/threonine

Genes: 207

Variants: serine/threonine

[Paragraph-level] PMCID: PMC1240052 Section: RESULTS PassageIndex: 13

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: L858R | Summary: The L858R mutant EGFR alters molecular function by constitutively activating STAT signaling pathways and increasing STAT3-dependent gene expression in transformed cells. Evidence Type: Oncogenic | Mutation: L858R | Summary: The L858R mutation in EGFR contributes to tumor development as evidenced by its transformation of NIH-3T3 cells and activation of oncogenic signaling pathways.

Gene→Variant (gene-first): 1956:L858R

Genes: 1956

Variants: L858R

[Paragraph-level] PMCID: PMC1240052 Section: RESULTS PassageIndex: 12

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: L858R | Summary: The L858R mutation in EGFR leads to constitutive phosphorylation of Shc, indicating an alteration in molecular function related to downstream signaling pathways. Evidence Type: Oncogenic | Mutation: L858R | Summary: The L858R mutation in EGFR contributes to tumor development by causing constitutive activation and signaling alterations in cancer cells.

Gene→Variant (gene-first): 1956:L858R

Genes: 1956

Variants: L858R

[Paragraph-level] PMCID: PMC1240052 Section: RESULTS PassageIndex: 10

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: L858R | Summary: The L858R mutation in EGFR is associated with ligand-independent autophosphorylation, indicating that it alters molecular function related to receptor activation. Evidence Type: Oncogenic | Mutation: L858R | Summary: The L858R mutation contributes to tumor development and progression, as it is implicated in the activation of EGFR in lung adenocarcinoma.

Gene→Variant (gene-first): 1956:L858R

Genes: 1956

Variants: L858R

[Paragraph-level] PMCID: PMC1240052 Section: RESULTS PassageIndex: 6

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: L858R | Summary: The L858R mutant form of EGFR was shown to enhance anchorage-independent growth in hTBE cells, indicating its role in tumor development. Evidence Type: Oncogenic | Mutation: G719S | Summary: The G719S mutant form of EGFR conferred enhanced anchorage-independent growth in hTBE cells, supporting its contribution to tumor progression. Evidence Type: Oncogenic | Mutation: L747_E749del A750P | Summary: The L747_E749del A750P deletion and insertion mutants formed colonies in soft agar with high efficiency, suggesting their oncogenic potential. Evidence Type: Oncogenic | Mutation: D770_N771insNPG | Summary: The D770_N771insNPG insertion mutant also demonstrated the ability to form colonies in soft agar, indicating its role in tumor development. Evidence Type: Oncogenic | Mutation: V12 | Summary: The expression of H-RAS V12 in hTBE cells was mentioned in the context of anchorage-independent growth, suggesting its oncogenic behavior, although it is not an EGFR mutation.

Gene→Variant (gene-first): 1956:D770_N771insNPG 1956:G719S 1956:L747_E749del A750P 1956:L858R 3265:V12

Genes: 1956 3265

Variants: D770_N771insNPG G719S L747_E749del A750P L858R V12

[Paragraph-level] PMCID: PMC1240052 Section: RESULTS PassageIndex: 5

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: A750P | Summary: The A750P mutation was assessed for transforming activity and was shown to contribute to tumor development by promoting colony formation in soft agar. Evidence Type: Oncogenic | Mutation: D770_N771insNPG | Summary: The D770_N771insNPG mutation demonstrated transforming activity, contributing to tumor development as indicated by increased colony formation efficiency in NIH-3T3 cells. Evidence Type: Oncogenic | Mutation: L747_E749del | Summary: The L747_E749del mutation was shown to have transforming activity, contributing to tumor development through enhanced colony formation in soft agar. Evidence Type: Oncogenic | Mutation: L858R | Summary: The L858R mutation exhibited transforming activity, as evidenced by its comparable colony formation efficiency to the deletion mutant in NIH-3T3 cells. Evidence Type: Oncogenic | Mutation: G719S | Summary: The G719S mutation was part of the study assessing transforming activity, indicating its role in tumor development through altered cellular behavior in focus formation assays.

Gene→Variant (gene-first): 1956:A750P 1956:D770_N771insNPG 1956:E749del 1956:G719S 1956:L858R

Genes: 1956

Variants: A750P D770_N771insNPG E749del G719S L858R

[Paragraph-level] PMCID: PMC1240052 Section: RESULTS PassageIndex: 4

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: L858R | Summary: The L858R EGFR mutation contributes to tumor development as demonstrated by the formation of tumors in immunocompromised mice after injection of transformed NIH-3T3 fibroblasts. Evidence Type: Oncogenic | Mutation: G719S | Summary: The G719S EGFR mutation contributes to tumor development as shown by the formation of tumors in immunocompromised mice following the injection of transformed NIH-3T3 fibroblasts. Evidence Type: Functional | Mutation: D837A | Summary: The D837A mutation is described as kinase-inactive, indicating an alteration in molecular function compared to the wild-type EGFR.

Gene→Variant (gene-first): 1956:D837A 1956:G719S 1956:L858R

Genes: 1956

Variants: D837A G719S L858R

[Paragraph-level] PMCID: PMC1240052 Section: RESULTS PassageIndex: 3

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: G719S | Summary: The G719S mutation was shown to transform NIH-3T3 cells to anchorage independence, indicating its role in tumor development. Evidence Type: Oncogenic | Mutation: L858R | Summary: The L858R mutation was able to transform NIH-3T3 cells to anchorage independence, demonstrating its contribution to tumor progression. Evidence Type: Functional | Mutation: D837A | Summary: The D837A mutation is described as kinase-dead and failed to induce colony formation, indicating an alteration in molecular function.

Gene→Variant (gene-first): 1956:D837A 1956:G719S 1956:L858R

Genes: 1956

Variants: D837A G719S L858R

[Paper-level Aggregated] PMCID: PMC1240052

Evidence Type(s): Functional

Summary: Mutation: D837A | Summary: The D837A mutation is described as kinase-dead and kinase-inactive, failing to induce colony formation, indicating an alteration in molecular function compared to the wild-type EGFR.

Evidence Type: Functional Mutation: L858R | Summary: The L858R mutation in EGFR is associated with ligand-independent autophosphorylation, constitutive phosphorylation of Shc, and constitutive activation of STAT signaling pathways, indicating alterations in molecular function related to receptor activation and downstream signaling pathways.

Evidence Type: Functional Mutation: mutant EGFR | Summary: The mutant EGFR leads to constitutive activation of signaling pathways, indicating an alteration in molecular function related to cell survival.

Gene→Variant (gene-first): EGFR(1956):D837A EGFR(1956):L858R NA:mutant EGFR

Genes: EGFR(1956) NA

Variants: D837A L858R mutant EGFR

[Paper-level Aggregated] PMCID: PMC1240052

Evidence Type(s): Oncogenic

Summary: Mutation: G719S | Summary: The G719S mutation contributes to tumor development by transforming NIH-3T3 cells to anchorage independence and promoting tumor formation in immunocompromised mice, indicating its role in altered cellular behavior and tumor progression.

Evidence Type: Oncogenic Mutation: L858R | Summary: The L858R mutation contributes to tumor development and progression by transforming NIH-3T3 cells, enhancing anchorage-independent growth, and activating oncogenic signaling pathways. It has been shown to form tumors in immunocompromised mice and is associated with constitutive activation of downstream signaling pathways.

Evidence Type: Oncogenic Mutation: A750P | Summary: The A750P mutation contributes to tumor development by promoting colony formation in soft agar, indicating its transforming activity.

Evidence Type: Oncogenic Mutation: D770_N771insNPG | Summary: The D770_N771insNPG mutation demonstrates transforming activity, contributing to tumor development as indicated by increased colony formation efficiency in NIH-3T3 cells.

Evidence Type: Oncogenic Mutation: L747_E749del | Summary: The L747_E749del mutation has transforming activity, contributing to tumor development through enhanced colony formation in soft agar.

Evidence Type: Oncogenic Mutation: L747_E749del A750P | Summary: The L747_E749del A750P deletion and insertion mutants formed colonies in soft agar with high efficiency, suggesting their oncogenic potential.

Evidence Type: Oncogenic Mutation: mutant EGFR | Summary: The mutant EGFR contributes to tumor development by activating downstream signaling pathways involved in promoting cell survival.

Gene→Variant (gene-first): EGFR(1956):G719S EGFR(1956):L858R EGFR(1956):A750P EGFR(1956):D770_N771insNPG NA:L747_E749del EGFR(1956):L747_E749del A750P NA:mutant EGFR

Genes: EGFR(1956) NA

Variants: G719S L858R A750P D770_N771insNPG L747_E749del L747_E749del A750P mutant EGFR

[Paper-level Aggregated] PMCID: PMC1240052

Evidence Type(s): Predictive

Summary: Mutation: G719S | Summary: The G719S mutation is associated with resistance to gefitinib, indicating its predictive value for therapy response in lung adenocarcinoma patients.

Evidence Type: Predictive Mutation: L747_E749del A750P | Summary: The L747_E749del A750P mutation correlates with sensitivity to gefitinib and erlotinib, supporting its predictive role in therapy response for lung adenocarcinoma.

Evidence Type: Predictive Mutation: L858R | Summary: The L858R mutation is linked to increased sensitivity to gefitinib and erlotinib, demonstrating its predictive significance for treatment outcomes in lung adenocarcinoma patients. Additionally, it is associated with a response to the irreversible EGFR inhibitor CL-387,785, which shows greater effectiveness compared to gefitinib or erlotinib in inhibiting colony formation and autophosphorylation.

Gene→Variant (gene-first): EGFR(1956):G719S EGFR(1956):L747_E749del A750P EGFR(1956):L858R

Genes: EGFR(1956)

Variants: G719S L747_E749del A750P L858R

[Paper-level Aggregated] PMCID: PMC1240052

Evidence Type(s): Oncogenic, Predictive, Functional

Justification: Oncogenic: The text describes how mutations such as L858R and G719S in the EGFR gene can transform NIH-3T3 cells, leading to anchorage independence and tumor formation in immunocompromised mice, indicating their oncogenic potential. Predictive: The presence of activating EGFR mutations, including L858R and G719S, is associated with clinical responses to EGFR inhibitors like gefitinib and erlotinib in lung adenocarcinoma patients, suggesting these mutations can predict treatment outcomes. Functional: The study demonstrates that mutant EGFRs, including L858R and G719S, exhibit constitutive activation of downstream signaling pathways, such as STAT3 and Akt, indicating functional alterations in signaling due to these mutations.

Gene→Variant (gene-first): EGFR(1956):A750P EGFR(1956):D770_N771insNPG EGFR(1956):E749del EGFR(1956):G719S EGFR(1956):L858R EGFR(1956):L747_E749del A750P HRAS(3265):V12 EGFR(1956):D837A AKT1(207):serine/threonine

Genes: EGFR(1956) HRAS(3265) AKT1(207)

Variants: A750P D770_N771insNPG E749del G719S L858R L747_E749del A750P V12 D837A serine/threonine

[Paragraph-level] PMCID: PMC1240052 Section: RESULTS PassageIndex: 19

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the effectiveness of the irreversible EGFR inhibitor CL-387,785 in inhibiting colony formation and autophosphorylation in cells expressing the L858R variant, indicating a correlation with treatment response. Oncogenic: The L858R variant is described in the context of its role in transformation assays, suggesting that it contributes to tumor development or progression.

Gene→Variant (gene-first): 1956:L858R

Genes: 1956

Variants: L858R

[Paragraph-level] PMCID: PMC1240052 Section: RESULTS PassageIndex: 16

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the correlation between the presence of activating EGFR mutations, including G719S, L747_E749del A750P, and L858R, and clinical responses to gefitinib or erlotinib, indicating their sensitivity to these therapies. Oncogenic: The passage describes the ability of the mentioned EGFR mutations to promote anchorage-independent growth in cell lines, which is indicative of their role in tumor development or progression.

Gene→Variant (gene-first): 1956:G719S 1956:L747_E749del A750P 1956:L858R

Genes: 1956

Variants: G719S L747_E749del A750P L858R

[Paragraph-level] PMCID: PMC1240052 Section: RESULTS PassageIndex: 14

Evidence Type(s): Functional

Justification: Functional: The passage discusses how the mutant EGFR leads to the constitutive activation of the serine/threonine kinase Akt, indicating an alteration in molecular function related to cell survival signaling pathways.

Gene→Variant (gene-first): 207:serine/threonine

Genes: 207

Variants: serine/threonine

[Paragraph-level] PMCID: PMC1240052 Section: RESULTS PassageIndex: 13

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage describes how the L858R mutant EGFR alters molecular function by activating STAT signaling pathways and increasing STAT3-dependent gene expression, as demonstrated through immunoblotting and reporter assays. Oncogenic: The L858R variant is associated with transformed NIH-3T3 cells, indicating its contribution to tumor development or progression.

Gene→Variant (gene-first): 1956:L858R

Genes: 1956

Variants: L858R

[Paragraph-level] PMCID: PMC1240052 Section: RESULTS PassageIndex: 12

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how the L858R variant of EGFR alters the molecular function of Shc binding and phosphorylation, indicating a change in biochemical activity associated with the mutant protein. Oncogenic: The L858R variant is described as contributing to constitutive activation of EGFR, which is associated with tumor development or progression, as evidenced by the downstream signaling alterations observed in the study.

Gene→Variant (gene-first): 1956:L858R

Genes: 1956

Variants: L858R

[Paragraph-level] PMCID: PMC1240052 Section: RESULTS PassageIndex: 10

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how the L858R variant alters the molecular function of EGFR, specifically its autophosphorylation activity in response to EGF stimulation, indicating a change in biochemical function. Oncogenic: The L858R variant is associated with tumor development, as it is mentioned in the context of a lung adenocarcinoma cell line, suggesting its role in cancer progression.

Gene→Variant (gene-first): 1956:L858R

Genes: 1956

Variants: L858R

[Paragraph-level] PMCID: PMC1240052 Section: RESULTS PassageIndex: 6

Evidence Type(s): Oncogenic, Functional

Justification: Oncogenic: The passage describes how the mutant forms of EGFR (L858R, G719S, L747_E749del A750P, and D770_N771insNPG) contribute to enhanced anchorage-independent growth in hTBE cells, indicating their role in tumor development or progression. Functional: The passage discusses the expression levels of the deletion and insertion mutants (L747_E749del A750P and D770_N771insNPG) and their ability to form colonies in soft agar, suggesting alterations in molecular function related to tumorigenesis.

Gene→Variant (gene-first): 1956:D770_N771insNPG 1956:G719S 1956:L747_E749del A750P 1956:L858R 3265:V12

Genes: 1956 3265

Variants: D770_N771insNPG G719S L747_E749del A750P L858R V12

[Paragraph-level] PMCID: PMC1240052 Section: RESULTS PassageIndex: 5

Evidence Type(s): Oncogenic

Justification: Oncogenic: The passage discusses how the EGFR variants A750P, D770_N771insNPG, L747_E749del, L858R, and G719S contribute to tumor development, as evidenced by their ability to form colonies in soft agar and exhibit loss of contact inhibition in NIH-3T3 cells.

Gene→Variant (gene-first): 1956:A750P 1956:D770_N771insNPG 1956:E749del 1956:G719S 1956:L858R

Genes: 1956

Variants: A750P D770_N771insNPG E749del G719S L858R

[Paragraph-level] PMCID: PMC1240052 Section: RESULTS PassageIndex: 4

Evidence Type(s): Oncogenic, Functional

Justification: Oncogenic: The passage describes how the L858R and G719S EGFR variants contribute to tumor development, as evidenced by their ability to transform NIH-3T3 cells and form tumors in immunocompromised mice. Functional: The passage indicates that the expression of the EGFR point mutants (L858R and G719S) in NIH-3T3 cells caused loss of contact inhibition, suggesting that these variants alter the molecular function of the EGFR protein.

Gene→Variant (gene-first): 1956:D837A 1956:G719S 1956:L858R

Genes: 1956

Variants: D837A G719S L858R

[Paragraph-level] PMCID: PMC1240052 Section: RESULTS PassageIndex: 3

Evidence Type(s): Oncogenic, Functional

Justification: Oncogenic: The passage discusses the ability of the G719S and L858R mutations to transform NIH-3T3 cells, indicating that these somatic variants contribute to tumor development. Functional: The passage describes how the mutations G719S and L858R alter the ability of EGFR to induce colony formation in soft agar, demonstrating a change in molecular function related to tumorigenesis.

Gene→Variant (gene-first): 1956:D837A 1956:G719S 1956:L858R

Genes: 1956

Variants: D837A G719S L858R