[Paper-level Aggregated] PMCID: PMC6478919

Evidence Type(s): Predictive, Functional, Prognostic

Justification: Predictive: The variation at position 21 of the BCL2 sequence (+21 T > C) predicts response to paclitaxel treatment, as patients with the T variant showed resistance while those with the C variant were more likely to respond. Functional: The T > C variant at location 21 of BCL2 alters RNA secondary structure and increases transcript stability, leading to higher BCL2 protein levels, which is functionally relevant in the context of treatment response. Prognostic: The presence of the T variant at location 21 is associated with a poorer treatment outcome, as indicated by the higher percentage of patients with this variant who required multiple lines of therapy compared to those with the C variant.

Gene→Variant (gene-first): BCL2(596):(AUC) of 39 BCL2(596):rs1801018 BCL2(596):+ 21 T > C POTEF(728378):+ 23 C > T BCL2(596):C > T BCL2(596):T > C BCL2(596):T at position 21 BCL2(596):C instead of a T BCL2(596):C to a T BCL2(596):+21 C BCL2(596):+21 T POTEF(728378):+23 C > T BCL2(596):21 T > C BCL2(596):C to T BCL2(596):T > C variation at position 21 BCL2(596):T >C BCL2(596):T instead of a C BCL2(596):T to C TUBB1(81027):rs6070697

Genes: BCL2(596) POTEF(728378) TUBB1(81027)

Variants: (AUC) of 39 rs1801018 + 21 T > C + 23 C > T C > T T > C T at position 21 C instead of a T C to a T +21 C +21 T +23 C > T 21 T > C C to T T > C variation at position 21 T >C T instead of a C T to C rs6070697

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 28

Evidence Type(s): Predictive

Justification: Predictive: The passage discusses the association between the rs1801018 variant and response to different treatments, indicating a correlation with treatment sensitivity.

Gene→Variant (gene-first): 596:(AUC) of 39 596:rs1801018

Genes: 596

Variants: (AUC) of 39 rs1801018

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 26

Evidence Type(s): Predictive, Functional

Justification: Predictive: The passage discusses the study of BCL2 spatial expression patterns in relation to paclitaxel resistance, indicating a potential correlation between the 21 T > C variant and treatment response. Functional: The passage describes an immunofluorescence assay that assesses the localization patterns of the BCL2 variant, indicating an alteration in molecular function related to protein localization.

Gene→Variant (gene-first): 596:21 T > C

Genes: 596

Variants: 21 T > C

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 25

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses how the variant 21 T > C leads to higher BCL2 expression, which is associated with resistance to the therapy paclitaxel. Oncogenic: The variant 21 T > C is implicated in contributing to tumor behavior by leading to increased expression of BCL2, which is associated with resistance to treatment, indicating a role in tumor progression.

Gene→Variant (gene-first): 596:21 T > C

Genes: 596

Variants: 21 T > C

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 24

Evidence Type(s): Predictive, Functional

Justification: Predictive: The passage indicates that the presence of the 21 T > C variant correlates with increased abundance of transcripts when treated with paclitaxel, suggesting a relationship with treatment response. Functional: The mention of increased abundance of transcripts implies that the 21 T > C variant alters molecular function, likely affecting gene expression in response to paclitaxel.

Gene→Variant (gene-first): 596:21 T > C

Genes: 596

Variants: 21 T > C

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 22

Evidence Type(s): Predictive, Functional

Justification: Predictive: The passage discusses the in vitro sensitivity to paclitaxel in relation to the 21 T > C variant, indicating that this variant may influence the response to the therapy. Functional: The variant is shown to alter the stability of the BCL2 transcript, which may lead to higher protein levels, indicating a change in molecular function.

Gene→Variant (gene-first): 596:21 T > C

Genes: 596

Variants: 21 T > C

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 20

Evidence Type(s): Functional

Justification: Functional: The passage discusses how the 21 T > C variant may regulate the transcriptional activity of the BCL2 gene, indicating an alteration in molecular function as evidenced by the increase in BCL2 mRNA levels in lymphocytes.

Gene→Variant (gene-first): 596:21 T > C 596:C instead of a T

Genes: 596

Variants: 21 T > C C instead of a T

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 16

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how the + 21 T > C substitution alters BCL2 protein levels, indicating a change in molecular function due to the variant. Oncogenic: The context of the study involves ovarian cancer patients, and the variant is associated with increased BCL2 protein levels, which can contribute to tumor development or progression.

Gene→Variant (gene-first): 596:+ 21 T > C 596:C instead of a T

Genes: 596

Variants: + 21 T > C C instead of a T

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 15

Evidence Type(s): Functional

Justification: Functional: The passage indicates that changing T to C at a specific location alters protein levels, which demonstrates a change in molecular function.

Gene→Variant (gene-first): 596:T to C

Genes: 596

Variants: T to C

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 14

Evidence Type(s): Functional

Justification: Functional: The passage discusses how the T > C variant alters the stability of BCL2 mRNA transcripts, indicating a change in molecular function.

Gene→Variant (gene-first): 596:T > C

Genes: 596

Variants: T > C

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 13

Evidence Type(s): Functional

Justification: Functional: The passage discusses how sequence modifications of BCL2 variants affect transcript stability and expression levels, indicating that the variants alter molecular function.

Gene→Variant (gene-first): 596:+21 C 596:+21 T 728378:+23 C > T 596:T > C

Genes: 596 728378

Variants: +21 C +21 T +23 C > T T > C

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 12

Evidence Type(s): Functional

Justification: Functional: The variant C to T alters the molecular function by stabilizing the BCL2 RNA secondary structure, as indicated by the in vitro analysis.

Gene→Variant (gene-first): 596:C to T

Genes: 596

Variants: C to T

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 11

Evidence Type(s): Functional

Justification: Functional: The passage discusses how the C > T change in BCL2 alters the mRNA structural ensemble, indicating that the variant affects molecular function related to RNA structure.

Gene→Variant (gene-first): 596:+ 21 T > C 728378:+ 23 C > T 596:C > T 596:T > C 596:T at position 21

Genes: 596 728378

Variants: + 21 T > C + 23 C > T C > T T > C T at position 21

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 9

Evidence Type(s): Functional

Justification: Functional: The passage indicates that the T > C variant alters the RNA secondary structure of BCL2, which is a change in molecular function.

Gene→Variant (gene-first): 596:T >C

Genes: 596

Variants: T >C

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 7

Evidence Type(s): Predictive, Diagnostic

Justification: Predictive: The passage discusses how the variant rs1801018 correlates with patient resistance to paclitaxel, indicating its predictive value for treatment response. Diagnostic: The variation is associated with the classification of patients based on their treatment response, helping to define which patients are likely to respond to single or multiple lines of therapy.

Gene→Variant (gene-first): 596:T instead of a C 596:rs1801018

Genes: 596

Variants: T instead of a C rs1801018

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 6

Evidence Type(s): Predictive

Justification: Predictive: The passage indicates that the variant + 21 T > C is associated with resistance to paclitaxel, which correlates the variant with treatment response.

Gene→Variant (gene-first): 596:+ 21 T > C 596:C to a T

Genes: 596

Variants: + 21 T > C C to a T

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 5

Evidence Type(s): Diagnostic

Justification: Diagnostic: The variant rs6070697 is discussed in the context of its distribution among treatment groups and its presence in both patients and controls, indicating its association with the study population and suggesting a role in defining or classifying the patient cohort.

Gene→Variant (gene-first): 81027:rs6070697

Genes: 81027

Variants: rs6070697

[Paragraph-level] PMCID: PMC6478919 Section: RESULTS PassageIndex: 2

Evidence Type(s): Predictive

Justification: Predictive: The passage states that the T > C variation at position 21 of the BCL2 sequence predicts response to paclitaxel, indicating a correlation with treatment response.

Gene→Variant (gene-first): 596:T > C variation at position 21

Genes: 596

Variants: T > C variation at position 21