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    1. Genomic Aberrations in Crizotinib Resistant Lung Adenocarcinoma Samples Identified by Transcriptome Sequencing

      [Paper-level Aggregated] PMCID: PMC4821611

      Evidence Type(s): Oncogenic, Predictive

      Justification: Oncogenic: The presence of ALK mutations (p.C1156Y and p.G1269A) in post-treatment tumor samples indicates their role in conferring resistance to crizotinib, suggesting an oncogenic function in the context of non-small cell lung cancer. Predictive: The identification of specific ALK mutations associated with resistance to crizotinib suggests that these mutations can predict treatment outcomes in patients with ALK-positive non-small cell lung cancer.

      Gene→Variant (gene-first): ALK(238):c.3467G>A ALK(238):c.3806G>C ALK(238):p.C1156Y ALK(238):p.G1269A

      Genes: ALK(238)

      Variants: c.3467G>A c.3806G>C p.C1156Y p.G1269A

    2. ALK-break positive non-small cell lung cancer (NSCLC) patients initially respond to crizotinib, but resistance occurs inevitably. In this study we aimed to identify fusion genes in crizotinib resistant tumor samples. Re-

      [Paragraph-level] PMCID: PMC4821611 Section: ABSTRACT PassageIndex: 1

      Evidence Type(s): Predictive, Oncogenic

      Justification: Predictive: The passage discusses ALK mutations (p.C1156Y and p.G1269A) in the context of crizotinib resistance, indicating a correlation between these variants and resistance to the therapy. Oncogenic: The ALK mutations are described as being detected in post-treatment tumor samples, suggesting their contribution to tumor development or progression in the context of crizotinib resistance.

      Gene→Variant (gene-first): 238:p.C1156Y 238:p.G1269A

      Genes: 238

      Variants: p.C1156Y p.G1269A

    3. Mutations in ALK, EGFR and KRAS have been reported to confer resistance against crizotinib. To determine presence of mutations in these genes in the three post-treatment samples, we inspected the RNA-seq bam files in IGV

      [Paragraph-level] PMCID: PMC4821611 Section: RESULTS PassageIndex: 10

      Evidence Type(s): Predictive, Oncogenic

      Justification: Predictive: The passage discusses mutations in the ALK gene, specifically p.C1156Y and p.G1269A, which have been reported to confer resistance against crizotinib, indicating a correlation with treatment response. Oncogenic: The presence of mutations in the ALK gene, such as p.C1156Y and p.G1269A, suggests that these somatic variants contribute to tumor development or progression, as they were identified in post-treatment tumor samples.

      Gene→Variant (gene-first): 238:c.3467G>A 238:c.3806G>C 238:p.C1156Y 238:p.G1269A

      Genes: 238

      Variants: c.3467G>A c.3806G>C p.C1156Y p.G1269A

    4. ALK-break positive non-small cell lung cancer (NSCLC) patients initially respond to crizotinib, but resistance occurs inevitably. In this study we aimed to identify fusion genes in crizotinib resistant tumor samples. Re-

      [Paragraph-level] PMCID: PMC4821611 Section: ABSTRACT PassageIndex: 1

      Evidence Type(s): Predictive, Oncogenic

      Justification: Predictive: The passage discusses ALK mutations (p.C1156Y and p.G1269A) in the context of crizotinib resistance, indicating a correlation between these variants and resistance to the therapy. Oncogenic: The ALK mutations are described as being detected in post-treatment tumor samples, suggesting their contribution to tumor development or progression in the context of crizotinib resistance.

      Gene→Variant (gene-first): 238:p.C1156Y 238:p.G1269A

      Genes: 238

      Variants: p.C1156Y p.G1269A

    5. Mutations in ALK, EGFR and KRAS have been reported to confer resistance against crizotinib. To determine presence of mutations in these genes in the three post-treatment samples, we inspected the RNA-seq bam files in IGV

      [Paragraph-level] PMCID: PMC4821611 Section: RESULTS PassageIndex: 10

      Evidence Type(s): Predictive, Oncogenic

      Justification: Predictive: The passage discusses mutations in the ALK gene, specifically p.C1156Y and p.G1269A, which have been reported to confer resistance against crizotinib, indicating a correlation with treatment response. Oncogenic: The presence of mutations in the ALK gene, such as p.C1156Y and p.G1269A, suggests that these somatic variants contribute to tumor development or progression, as they were identified in post-treatment tumor samples.

      Gene→Variant (gene-first): 238:c.3467G>A 238:c.3806G>C 238:p.C1156Y 238:p.G1269A

      Genes: 238

      Variants: c.3467G>A c.3806G>C p.C1156Y p.G1269A