[Paper-level Aggregated] PMCID: PMC9859631

Evidence Type(s): Oncogenic

Summary: Mutation: c.1899-880_1946+761del | Summary: The variant c.1899-880_1946+761del was detected in two patients, indicating its potential role in tumor development or progression.

Evidence Type: Oncogenic Mutation: L858R | Summary: The L858R mutation contributes to tumor development in advanced LUAD and is relevant for predicting response to osimertinib therapy.

Evidence Type: Oncogenic Mutation: L755S | Summary: The L755S mutation is suggested as a potential resistance mechanism in the context of osimertinib treatment.

Evidence Type: Oncogenic Mutation: D769Y | Summary: The D769Y mutation is indicated as a possible resistance mechanism following treatment with osimertinib.

Evidence Type: Oncogenic Mutation: c.1899-32_1909del | Summary: The c.1899-32_1909del alteration is detected as a concurrent alteration in the context of resistance mechanisms after osimertinib progression.

Evidence Type: Oncogenic Mutation: D1288N | Summary: The D1288N mutation is associated with MET TKI resistance, indicating its role in tumor development or progression.

Evidence Type: Oncogenic Mutation: L1195I | Summary: The L1195I mutation is known as a secondary mutation associated with MET TKI resistance, contributing to tumor progression.

Evidence Type: Oncogenic Mutation: L1195V | Summary: The L1195V mutation is recognized as a secondary mutation linked to MET TKI resistance, playing a role in tumor development.

Evidence Type: Oncogenic Mutation: Y1230H | Summary: The Y1230H mutation is identified as a secondary mutation associated with MET TKI resistance, indicating its contribution to tumor progression.

Gene→Variant (gene-first): ERBB2(2064):c.1899-880_1946+761del EGFR(1956):L858R ERBB2(2064):L755S ERBB2(2064):D769Y ERBB2(2064):c.1899-32_1909del NA:D1288N NA:L1195I SLTM(79811):L1195V SLTM(79811):Y1230H

Genes: ERBB2(2064) EGFR(1956) NA SLTM(79811)

Variants: c.1899-880_1946+761del L858R L755S D769Y c.1899-32_1909del D1288N L1195I L1195V Y1230H

[Paper-level Aggregated] PMCID: PMC9859631

Evidence Type(s): Predictive

Summary: Mutation: c.1899-2A>G | Summary: The variant c.1899-2A>G was identified in a patient after treatment, suggesting a correlation with treatment response or resistance.

Evidence Type: Predictive Mutation: L858R | Summary: The L858R mutation in EGFR is associated with advanced LUAD and is relevant for predicting response to osimertinib therapy.

Gene→Variant (gene-first): ERBB2(2064):c.1899-2A>G EGFR(1956):L858R

Genes: ERBB2(2064) EGFR(1956)

Variants: c.1899-2A>G L858R

[Paragraph-level] PMCID: PMC9859631 Section: RESULTS PassageIndex: 12

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: D1288N | Summary: The D1288N mutation is associated with MET TKI resistance, indicating its role in tumor development or progression. Evidence Type: Oncogenic | Mutation: L1195I | Summary: The L1195I mutation is known as a secondary mutation associated with MET TKI resistance, contributing to tumor progression. Evidence Type: Oncogenic | Mutation: L1195V | Summary: The L1195V mutation is recognized as a secondary mutation linked to MET TKI resistance, playing a role in tumor development. Evidence Type: Oncogenic | Mutation: Y1230H | Summary: The Y1230H mutation is identified as a secondary mutation associated with MET TKI resistance, indicating its contribution to tumor progression.

Gene→Variant (gene-first): 79811:D1288N L1195I 79811:L1195V 79811:Y1230H 2064:c.1899-936_1946+520del

Genes: 79811 2064

Variants: D1288N L1195I L1195V Y1230H c.1899-936_1946+520del

[Paragraph-level] PMCID: PMC9859631 Section: RESULTS PassageIndex: 11

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: L858R | Summary: The L858R mutation in EGFR is associated with advanced LUAD and is relevant for predicting response to osimertinib therapy. Evidence Type: Oncogenic | Mutation: L858R | Summary: The L858R mutation contributes to tumor development in advanced LUAD. Evidence Type: Oncogenic | Mutation: L755S | Summary: The L755S mutation is suggested as a potential resistance mechanism in the context of osimertinib treatment. Evidence Type: Oncogenic | Mutation: D769Y | Summary: The D769Y mutation is indicated as a possible resistance mechanism following treatment with osimertinib. Evidence Type: Oncogenic | Mutation: c.1899-32_1909del | Summary: The c.1899-32_1909del alteration is detected as a concurrent alteration in the context of resistance mechanisms after osimertinib progression.

Gene→Variant (gene-first): 2064:D769Y 2064:L755S 1956:L858R 2064:c.1899-32_1909del

Genes: 2064 1956

Variants: D769Y L755S L858R c.1899-32_1909del

[Paragraph-level] PMCID: PMC9859631 Section: RESULTS PassageIndex: 5

Evidence Type(s): Oncogenic, Predictive

Summary: Evidence Type: Oncogenic | Mutation: c.1899-880_1946+761del | Summary: The variant c.1899-880_1946+761del was detected in two patients, indicating its potential role in tumor development or progression. Evidence Type: Predictive | Mutation: c.1899-2A>G | Summary: The variant c.1899-2A>G was identified in a patient after treatment, suggesting a correlation with treatment response or resistance.

Gene→Variant (gene-first): 2064:c.1899-2A>G 2064:c.1899-880_1946+761del

Genes: 2064

Variants: c.1899-2A>G c.1899-880_1946+761del

[Paper-level Aggregated] PMCID: PMC9859631

Evidence Type(s): Oncogenic, Predictive, Functional

Justification: Oncogenic: The text describes various ERBB2 alterations, including ERBB2DeltaEx16 variants, which are suggested to play a role in resistance to targeted therapies, indicating their potential oncogenic nature. Predictive: The presence of specific mutations such as L858R, L755S, D769Y, and others in the context of treatment resistance suggests that these variants may predict response to therapies and disease progression. Functional: The identification of multiple ERBB2 alterations and their association with resistance mechanisms implies that these variants may have functional consequences on the gene's activity and its role in cancer progression.

Gene→Variant (gene-first): SLTM(79811):D1288N L1195I SLTM(79811):L1195V SLTM(79811):Y1230H ERBB2(2064):c.1899-936_1946+520del ERBB2(2064):D769Y ERBB2(2064):L755S EGFR(1956):L858R ERBB2(2064):c.1899-32_1909del ERBB2(2064):c.1899-2A>G ERBB2(2064):c.1899-880_1946+761del

Genes: SLTM(79811) ERBB2(2064) EGFR(1956)

Variants: D1288N L1195I L1195V Y1230H c.1899-936_1946+520del D769Y L755S L858R c.1899-32_1909del c.1899-2A>G c.1899-880_1946+761del

[Paragraph-level] PMCID: PMC9859631 Section: RESULTS PassageIndex: 12

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses various mutations, including Y1230H, D1288N L1195I, and L1195V, which are described as secondary mutations associated with MET TKI resistance, indicating a correlation with treatment response. Oncogenic: The mention of mutations contributing to resistance against targeted therapies suggests that these variants may play a role in tumor development or progression, particularly in the context of lung cancer.

Gene→Variant (gene-first): 79811:D1288N L1195I 79811:L1195V 79811:Y1230H 2064:c.1899-936_1946+520del

Genes: 79811 2064

Variants: D1288N L1195I L1195V Y1230H c.1899-936_1946+520del

[Paragraph-level] PMCID: PMC9859631 Section: RESULTS PassageIndex: 11

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the presence of the EGFR L858R variant in a patient with advanced LUAD and its association with resistance to osimertinib, indicating a correlation with treatment response. Oncogenic: The mention of the EGFR L858R variant and its role in the context of advanced LUAD suggests that it contributes to tumor development or progression, particularly as it is associated with resistance mechanisms.

Gene→Variant (gene-first): 2064:D769Y 2064:L755S 1956:L858R 2064:c.1899-32_1909del

Genes: 2064 1956

Variants: D769Y L755S L858R c.1899-32_1909del

[Paragraph-level] PMCID: PMC9859631 Section: RESULTS PassageIndex: 5

Evidence Type(s): Diagnostic, Predictive

Justification: Diagnostic: The passage discusses the detection of ERBB2 variants in patients, indicating their association with specific cases, which supports their use in defining or classifying a disease subtype. Predictive: The mention of the novel variant ERBB2 c.1899-2A>G being detected after treatment suggests a potential correlation with treatment response, indicating its relevance in predicting therapy outcomes.

Gene→Variant (gene-first): 2064:c.1899-2A>G 2064:c.1899-880_1946+761del

Genes: 2064

Variants: c.1899-2A>G c.1899-880_1946+761del

[Paragraph-level] PMCID: PMC9859631 Section: RESULTS PassageIndex: 12

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses various mutations, including Y1230H, D1288N L1195I, and L1195V, which are described as secondary mutations associated with MET TKI resistance, indicating a correlation with treatment response. Oncogenic: The mention of mutations contributing to resistance against targeted therapies suggests that these variants may play a role in tumor development or progression, particularly in the context of lung cancer.

Gene→Variant (gene-first): 79811:D1288N L1195I 79811:L1195V 79811:Y1230H 2064:c.1899-936_1946+520del

Genes: 79811 2064

Variants: D1288N L1195I L1195V Y1230H c.1899-936_1946+520del

[Paragraph-level] PMCID: PMC9859631 Section: RESULTS PassageIndex: 11

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the presence of the EGFR L858R variant in a patient with advanced LUAD and its association with resistance to osimertinib, indicating a correlation with treatment response. Oncogenic: The mention of the EGFR L858R variant and its role in the context of advanced LUAD suggests that it contributes to tumor development or progression, particularly as it is associated with resistance mechanisms.

Gene→Variant (gene-first): 2064:D769Y 2064:L755S 1956:L858R 2064:c.1899-32_1909del

Genes: 2064 1956

Variants: D769Y L755S L858R c.1899-32_1909del

[Paragraph-level] PMCID: PMC9859631 Section: RESULTS PassageIndex: 5

Evidence Type(s): Diagnostic, Predictive

Justification: Diagnostic: The passage discusses the detection of ERBB2 variants in patients, indicating their association with specific cases, which supports their use in defining or classifying a disease subtype. Predictive: The mention of the novel variant ERBB2 c.1899-2A>G being detected after treatment suggests a potential correlation with treatment response, indicating its relevance in predicting therapy outcomes.

Gene→Variant (gene-first): 2064:c.1899-2A>G 2064:c.1899-880_1946+761del

Genes: 2064

Variants: c.1899-2A>G c.1899-880_1946+761del