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    1. karim2001khoury 19 Feb 2026
      Mutant Fibroblast Growth Factor Receptor 3 Induces Intracellular Signaling and Cellular Transformation in a Cell Type- and Mutation-Specific Manner

      [Paper-level Aggregated] PMCID: PMC2789045

      Evidence Type(s): Oncogenic, Functional, Predictive

      Justification: Oncogenic: The evidence indicates that mutations S249C, Y375C, and K652E in FGFR3 lead to increased cell proliferation, morphological transformation, and anchorage-independent growth, suggesting that these mutations contribute to oncogenic processes in bladder tumors. Functional: The study demonstrates that the FGFR3 mutations affect signaling pathways and cellular behaviors, such as phosphorylation of downstream effectors and changes in cell cycle profiles, indicating a functional impact of these mutations on urothelial cells. Predictive: The differential effects of the FGFR3 mutations on cell proliferation and viability suggest that the presence of specific mutations like S249C and Y375C may predict the behavior of bladder cancer cells in response to growth conditions and treatments.

      Gene→Variant (gene-first): FGFR3(2261):K652E FGFR3(2261):S249C FGFR3(2261):Y375C FGFR3(2261):Y762F

      Genes: FGFR3(2261)

      Variants: K652E S249C Y375C Y762F

      CIViC paper-level aggregated PMC2789045
    2. karim2001khoury 19 Feb 2026
      In TERT-NHUC, abolishing PLCgamma1 phosphorylation significantly reduced the increase in saturation density associated with S249C FGFR3 (13% vs. 24%, p=0.05) (Figure 6a), suggesting that PLCgamma1 signaling contributes t

      [Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 23

      Evidence Type(s): Functional, Oncogenic

      Justification: Functional: The passage discusses how the S249C and K652E mutations affect cell viability and signaling pathways, indicating that these variants alter molecular or biochemical functions related to cell growth and density. Oncogenic: The evidence suggests that the S249C and K652E mutations contribute to tumor development or progression by affecting cell cycle phases and viability, which are indicative of cancer-driving behavior.

      Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y762F

      Genes: 2261

      Variants: K652E S249C Y762F

      CIViC paragraph-level PMC2789045 Functional Oncogenic
    3. karim2001khoury 19 Feb 2026
      To clarify whether the lack of constitutive PLCgamma1 phosphorylation may explain the different phenotypic behavior associated with the K652E mutation, we used a construct encoding a S249C FGFR3 protein with a mutated PL

      [Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 22

      Evidence Type(s): Oncogenic, Functional

      Justification: Oncogenic: The passage discusses the S249C+Y762F FGFR3 mutant protein's ability to induce morphological transformation and increased proliferation in NIH-3T3 cells, indicating its role in tumor development or progression. Functional: The passage describes how the S249C+Y762F mutation affects the phosphorylation of PLCgamma1 and alters the activation of downstream signaling pathways, demonstrating a change in molecular function.

      Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y762F

      Genes: 2261

      Variants: K652E S249C Y762F

      CIViC paragraph-level PMC2789045 Oncogenic Functional
    4. karim2001khoury 19 Feb 2026
      As expected, FGF1 induced phosphorylation of FRS2alpha, ERK1/2 and PLCgamma1 in normal urothelial cells over-expressing wildtype FGFR3 (Figure 4b). Consistent with their complete ligand-independence, FGF1 treatment faile

      [Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 20

      Evidence Type(s): Functional, Oncogenic

      Justification: Functional: The passage discusses how the K652E, S249C, and Y375C mutations alter the signaling response to FGF1 treatment, indicating that these variants affect molecular function related to phosphorylation and activation of signaling pathways. Oncogenic: The context of the mutations being discussed in relation to their effects on signaling pathways suggests that they may contribute to tumor development or progression, particularly given the focus on their responses in cancer-related cellular contexts.

      Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

      Genes: 2261

      Variants: K652E S249C Y375C

      CIViC paragraph-level PMC2789045 Functional Oncogenic
    5. karim2001khoury 19 Feb 2026
      We next examined whether cells expressing wildtype and mutant FGFR3 were responsive to FGF1 stimulation in terms of receptor activation (Figure 4a, Supplementary Figure 5) and signaling (Figure 4b, Supplementary Figure 5

      [Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 19

      Evidence Type(s): Predictive, Functional

      Justification: Predictive: The passage discusses the response of cells expressing mutant FGFR3 variants (S249C, Y375C, K652E) to FGF1 stimulation, indicating a correlation with receptor activation and signaling, which relates to treatment response. Functional: The passage describes how the variants S249C, Y375C, and K652E affect the phosphorylation of FGFR3, indicating that these mutations alter the molecular function of the receptor in response to ligand stimulation.

      Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

      Genes: 2261

      Variants: K652E S249C Y375C

      CIViC paragraph-level PMC2789045 Predictive Functional
    6. karim2001khoury 19 Feb 2026
      Signaling was examined in cells at various degrees of confluence, in full and depleted medium (Figure 3c, Supplementary Figure 4b). In all conditions tested, no differences were observed between mutant and control cells

      [Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 16

      Evidence Type(s): Functional, Oncogenic

      Justification: Functional: The passage discusses the increased phosphorylation of PLCgamma1 specifically in cells expressing the S249C and Y375C FGFR3 variants, indicating that these variants alter molecular function. Oncogenic: The mention of increased phosphorylation of signaling proteins in cells expressing the FGFR3 mutants suggests that these variants contribute to tumor development or progression.

      Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

      Genes: 2261

      Variants: K652E S249C Y375C

      CIViC paragraph-level PMC2789045 Functional Oncogenic
    7. karim2001khoury 19 Feb 2026
      To investigate the reason for the differential behavior of cells expressing K652E FGFR3, we assessed the phosphorylation levels of FGFR3 mutant proteins and downstream effectors in urothelial cells. All mutant forms of F

      [Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 15

      Evidence Type(s): Functional, Oncogenic

      Justification: Functional: The passage discusses how the K652E, S249C, and Y375C variants of FGFR3 alter phosphorylation levels and dimerization behavior, indicating changes in molecular function. Oncogenic: The variants are described in the context of their constitutive activation and behavior in urothelial cells, suggesting their role in tumor development or progression.

      Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

      Genes: 2261

      Variants: K652E S249C Y375C

      CIViC paragraph-level PMC2789045 Functional Oncogenic
    8. karim2001khoury 19 Feb 2026
      Three proteins involved in cell survival, MCL1, BCL-XL, and BCL2, were up-regulated in confluent cells expressing all types of mutant FGFR3 (Figure 2d, Supplementary Figure 3b). Surprisingly, there was no difference in t

      [Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 13

      Evidence Type(s): Functional, Oncogenic

      Justification: Functional: The passage discusses the expression of proteins involved in cell survival and suggests that the K652E variant may alter the viability of cells, indicating a change in molecular function. Oncogenic: The context implies that the K652E variant contributes to tumor behavior by affecting cell viability, which is a characteristic of oncogenic variants.

      Gene→Variant (gene-first): 2261:K652E

      Genes: 2261

      Variants: K652E

      CIViC paragraph-level PMC2789045 Functional Oncogenic
    9. karim2001khoury 19 Feb 2026
      Consistent with their altered cell cycle profile, confluent TERT-NHUC expressing mutant FGFR3 exhibited changes in cell cycle-related proteins (Figure 2d, Supplementary Figure 3a). Whilst in control cells the expression

      [Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 12

      Evidence Type(s): Functional

      Justification: Functional: The passage discusses how the variants S249C, Y375C, and K652E FGFR3 alter the expression and phosphorylation of cell cycle-related proteins, indicating a change in molecular function.

      Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

      Genes: 2261

      Variants: K652E S249C Y375C

      CIViC paragraph-level PMC2789045 Functional
    10. karim2001khoury 19 Feb 2026
      Cells expressing S249C and Y375C FGFR3 were significantly more viable at confluence compared to controls or cells expressing wildtype FGFR3 (p<=0.001). On days 12 (Figure 2c) and 15 (data not shown), on average 45% of S2

      [Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 10

      Evidence Type(s): Functional, Oncogenic

      Justification: Functional: The passage discusses the viability of cells expressing specific variants (S249C and Y375C) compared to controls, indicating that these variants alter the molecular or biochemical function of FGFR3, affecting cell viability. Oncogenic: The evidence suggests that the variants S249C and Y375C contribute to tumor development or progression by enhancing cell viability, which is a characteristic of oncogenic behavior.

      Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

      Genes: 2261

      Variants: K652E S249C Y375C

      CIViC paragraph-level PMC2789045 Functional Oncogenic
    11. karim2001khoury 19 Feb 2026
      In controls, the number of cells in the G0/G1 phase of the cell cycle progressively increased at confluence, while the number of viable cells decreased. No significant differences in cell cycle profile or viability were

      [Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 9

      Evidence Type(s): Functional

      Justification: Functional: The mention of K652E and Y375C variants also suggests alterations in cell cycle profiles, indicating a change in molecular function related to cell cycle dynamics.

      Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

      Genes: 2261

      Variants: K652E S249C Y375C

      CIViC paragraph-level PMC2789045 Functional
    12. karim2001khoury 19 Feb 2026
      The saturation density of cells expressing K652E FGFR3 was similar to controls and cells expressing wildtype FGFR3 or S249C KD. Therefore, the magnitude of the phenotypic effect was of the order S249C>Y375C>K652E=Wildtyp

      [Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 6

      Evidence Type(s): Diagnostic, Functional

      Justification: Diagnostic: The passage discusses the relative frequencies of the mutations K652E, S249C, and Y375C in bladder tumors, indicating an association with the disease. Functional: The passage mentions the phenotypic effects of the variants, suggesting that they alter the behavior of cells expressing these mutations compared to controls.

      Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

      Genes: 2261

      Variants: K652E S249C Y375C

      CIViC paragraph-level PMC2789045 Diagnostic Functional
    13. karim2001khoury 19 Feb 2026
      Next we studied the effects of mutant FGFR3 in normal urothelial cells by expressing S249C, Y375C and K652E FGFR3 in TERT-NHUC. Expression levels were comparable to those observed in the bladder cancer cell line TCC97-7,

      [Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 5

      Evidence Type(s): Functional, Oncogenic

      Justification: Functional: The passage discusses how the expression of mutant FGFR3 variants S249C and Y375C alters the saturation density and morphology of normal urothelial cells, indicating a change in molecular or biochemical function. Oncogenic: The expression of the mutant FGFR3 variants is associated with changes in cell behavior, such as increased saturation density and altered morphology, which suggests a contribution to tumor development or progression.

      Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

      Genes: 2261

      Variants: K652E S249C Y375C

      CIViC paragraph-level PMC2789045 Functional Oncogenic
    14. karim2001khoury 19 Feb 2026
      Initially, we assessed the ability of three mutant forms of FGFR3 that are found in UC (S249C, Y375C, and K652E) to transform NIH-3T3 cells. In these cells, expression of all FGFR3 mutations resulted in a transformed spi

      [Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 3

      Evidence Type(s): Oncogenic, Functional

      Justification: Oncogenic: The passage discusses the ability of the FGFR3 mutations (S249C, Y375C, and K652E) to transform NIH-3T3 cells, indicating that these somatic variants contribute to tumor development or progression. Functional: The passage describes how the FGFR3 mutations alter molecular function, specifically through increased phosphorylation of various proteins and changes in cell morphology and proliferation, demonstrating their biochemical activity.

      Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

      Genes: 2261

      Variants: K652E S249C Y375C

      CIViC paragraph-level PMC2789045 Oncogenic Functional
    15. karim2001khoury 19 Feb 2026
      Although activating mutations of FGFR3 are frequent in bladder tumors, little information is available on their specific effects in urothelial cells or the basis for the observed mutation spectrum. We investigated the ph

      [Paragraph-level] PMCID: PMC2789045 Section: ABSTRACT PassageIndex: 1

      Evidence Type(s): Functional, Oncogenic

      Justification: Functional: The passage discusses how the FGFR3 mutations (S249C, Y375C, and K652E) alter molecular signaling pathways, specifically the phosphorylation of various proteins, indicating a change in biochemical function. Oncogenic: The passage describes how the mutant FGFR3 variants induce morphological transformation, cell proliferation, and anchorage-independent growth, which are indicative of their role in tumor development and progression.

      Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

      Genes: 2261

      Variants: K652E S249C Y375C

      CIViC paragraph-level PMC2789045 Functional Oncogenic
    16. karim2001khoury 19 Feb 2026
      In TERT-NHUC, abolishing PLCgamma1 phosphorylation significantly reduced the increase in saturation density associated with S249C FGFR3 (13% vs. 24%, p=0.05) (Figure 6a), suggesting that PLCgamma1 signaling contributes t

      [Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 23

      Evidence Type(s): Functional, Oncogenic

      Justification: Functional: The passage discusses how the S249C and K652E mutations affect cell viability and signaling pathways, indicating that these variants alter molecular or biochemical functions related to cell growth and density. Oncogenic: The evidence suggests that the S249C and K652E mutations contribute to tumor development or progression by affecting cell cycle phases and viability, which are indicative of cancer-driving behavior.

      Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y762F

      Genes: 2261

      Variants: K652E S249C Y762F

      CIViC paragraph-level PMC2789045 Functional Oncogenic
    17. karim2001khoury 19 Feb 2026
      To clarify whether the lack of constitutive PLCgamma1 phosphorylation may explain the different phenotypic behavior associated with the K652E mutation, we used a construct encoding a S249C FGFR3 protein with a mutated PL

      [Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 22

      Evidence Type(s): Oncogenic, Functional

      Justification: Oncogenic: The passage discusses the S249C+Y762F FGFR3 mutant protein's ability to induce morphological transformation and increased proliferation in NIH-3T3 cells, indicating its role in tumor development or progression. Functional: The passage describes how the S249C+Y762F mutation affects the phosphorylation of PLCgamma1 and alters the activation of downstream signaling pathways, demonstrating a change in molecular function.

      Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y762F

      Genes: 2261

      Variants: K652E S249C Y762F

      CIViC paragraph-level PMC2789045 Oncogenic Functional
    18. karim2001khoury 19 Feb 2026
      As expected, FGF1 induced phosphorylation of FRS2alpha, ERK1/2 and PLCgamma1 in normal urothelial cells over-expressing wildtype FGFR3 (Figure 4b). Consistent with their complete ligand-independence, FGF1 treatment faile

      [Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 20

      Evidence Type(s): Functional, Oncogenic

      Justification: Functional: The passage discusses how the K652E, S249C, and Y375C mutations alter the signaling response to FGF1 treatment, indicating that these variants affect molecular function related to phosphorylation and activation of signaling pathways. Oncogenic: The context of the mutations being discussed in relation to their effects on signaling pathways suggests that they may contribute to tumor development or progression, particularly given the focus on their responses in cancer-related cellular contexts.

      Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

      Genes: 2261

      Variants: K652E S249C Y375C

      CIViC paragraph-level PMC2789045 Functional Oncogenic
    19. karim2001khoury 19 Feb 2026
      We next examined whether cells expressing wildtype and mutant FGFR3 were responsive to FGF1 stimulation in terms of receptor activation (Figure 4a, Supplementary Figure 5) and signaling (Figure 4b, Supplementary Figure 5

      [Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 19

      Evidence Type(s): Predictive, Functional

      Justification: Predictive: The passage discusses the response of cells expressing mutant FGFR3 variants (S249C, Y375C, K652E) to FGF1 stimulation, indicating a correlation with receptor activation and signaling, which relates to treatment response. Functional: The passage describes how the variants S249C, Y375C, and K652E affect the phosphorylation of FGFR3, indicating that these mutations alter the molecular function of the receptor in response to ligand stimulation.

      Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

      Genes: 2261

      Variants: K652E S249C Y375C

      CIViC paragraph-level PMC2789045 Predictive Functional
    20. karim2001khoury 19 Feb 2026
      Signaling was examined in cells at various degrees of confluence, in full and depleted medium (Figure 3c, Supplementary Figure 4b). In all conditions tested, no differences were observed between mutant and control cells

      [Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 16

      Evidence Type(s): Functional, Oncogenic

      Justification: Functional: The passage discusses the increased phosphorylation of PLCgamma1 specifically in cells expressing the S249C and Y375C FGFR3 variants, indicating that these variants alter molecular function. Oncogenic: The mention of increased phosphorylation of signaling proteins in cells expressing the FGFR3 mutants suggests that these variants contribute to tumor development or progression.

      Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

      Genes: 2261

      Variants: K652E S249C Y375C

      CIViC paragraph-level PMC2789045 Functional Oncogenic
    21. karim2001khoury 19 Feb 2026
      To investigate the reason for the differential behavior of cells expressing K652E FGFR3, we assessed the phosphorylation levels of FGFR3 mutant proteins and downstream effectors in urothelial cells. All mutant forms of F

      [Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 15

      Evidence Type(s): Functional, Oncogenic

      Justification: Functional: The passage discusses how the K652E, S249C, and Y375C variants of FGFR3 alter phosphorylation levels and dimerization behavior, indicating changes in molecular function. Oncogenic: The variants are described in the context of their constitutive activation and behavior in urothelial cells, suggesting their role in tumor development or progression.

      Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

      Genes: 2261

      Variants: K652E S249C Y375C

      CIViC paragraph-level PMC2789045 Functional Oncogenic
    22. karim2001khoury 19 Feb 2026
      Three proteins involved in cell survival, MCL1, BCL-XL, and BCL2, were up-regulated in confluent cells expressing all types of mutant FGFR3 (Figure 2d, Supplementary Figure 3b). Surprisingly, there was no difference in t

      [Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 13

      Evidence Type(s): Functional, Oncogenic

      Justification: Functional: The passage discusses the expression of proteins involved in cell survival and suggests that the K652E variant may alter the viability of cells, indicating a change in molecular function. Oncogenic: The context implies that the K652E variant contributes to tumor behavior by affecting cell viability, which is a characteristic of oncogenic variants.

      Gene→Variant (gene-first): 2261:K652E

      Genes: 2261

      Variants: K652E

      CIViC paragraph-level PMC2789045 Functional Oncogenic
    23. karim2001khoury 19 Feb 2026
      Consistent with their altered cell cycle profile, confluent TERT-NHUC expressing mutant FGFR3 exhibited changes in cell cycle-related proteins (Figure 2d, Supplementary Figure 3a). Whilst in control cells the expression

      [Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 12

      Evidence Type(s): Functional

      Justification: Functional: The passage discusses how the variants S249C, Y375C, and K652E FGFR3 alter the expression and phosphorylation of cell cycle-related proteins, indicating a change in molecular function.

      Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

      Genes: 2261

      Variants: K652E S249C Y375C

      CIViC paragraph-level PMC2789045 Functional
    24. karim2001khoury 19 Feb 2026
      Cells expressing S249C and Y375C FGFR3 were significantly more viable at confluence compared to controls or cells expressing wildtype FGFR3 (p<=0.001). On days 12 (Figure 2c) and 15 (data not shown), on average 45% of S2

      [Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 10

      Evidence Type(s): Functional, Oncogenic

      Justification: Functional: The passage discusses the viability of cells expressing specific variants (S249C and Y375C) compared to controls, indicating that these variants alter the molecular or biochemical function of FGFR3, affecting cell viability. Oncogenic: The evidence suggests that the variants S249C and Y375C contribute to tumor development or progression by enhancing cell viability, which is a characteristic of oncogenic behavior.

      Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

      Genes: 2261

      Variants: K652E S249C Y375C

      CIViC paragraph-level PMC2789045 Functional Oncogenic
    25. karim2001khoury 19 Feb 2026
      In controls, the number of cells in the G0/G1 phase of the cell cycle progressively increased at confluence, while the number of viable cells decreased. No significant differences in cell cycle profile or viability were

      [Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 9

      Evidence Type(s): Functional

      Justification: Functional: The mention of K652E and Y375C variants also suggests alterations in cell cycle profiles, indicating a change in molecular function related to cell cycle dynamics.

      Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

      Genes: 2261

      Variants: K652E S249C Y375C

      CIViC paragraph-level PMC2789045 Functional
    26. karim2001khoury 19 Feb 2026
      The saturation density of cells expressing K652E FGFR3 was similar to controls and cells expressing wildtype FGFR3 or S249C KD. Therefore, the magnitude of the phenotypic effect was of the order S249C>Y375C>K652E=Wildtyp

      [Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 6

      Evidence Type(s): Diagnostic, Functional

      Justification: Diagnostic: The passage discusses the relative frequencies of the mutations K652E, S249C, and Y375C in bladder tumors, indicating an association with the disease. Functional: The passage mentions the phenotypic effects of the variants, suggesting that they alter the behavior of cells expressing these mutations compared to controls.

      Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

      Genes: 2261

      Variants: K652E S249C Y375C

      CIViC paragraph-level PMC2789045 Diagnostic Functional
    27. karim2001khoury 19 Feb 2026
      Next we studied the effects of mutant FGFR3 in normal urothelial cells by expressing S249C, Y375C and K652E FGFR3 in TERT-NHUC. Expression levels were comparable to those observed in the bladder cancer cell line TCC97-7,

      [Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 5

      Evidence Type(s): Functional, Oncogenic

      Justification: Functional: The passage discusses how the expression of mutant FGFR3 variants S249C and Y375C alters the saturation density and morphology of normal urothelial cells, indicating a change in molecular or biochemical function. Oncogenic: The expression of the mutant FGFR3 variants is associated with changes in cell behavior, such as increased saturation density and altered morphology, which suggests a contribution to tumor development or progression.

      Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

      Genes: 2261

      Variants: K652E S249C Y375C

      CIViC paragraph-level PMC2789045 Functional Oncogenic
    28. karim2001khoury 19 Feb 2026
      Initially, we assessed the ability of three mutant forms of FGFR3 that are found in UC (S249C, Y375C, and K652E) to transform NIH-3T3 cells. In these cells, expression of all FGFR3 mutations resulted in a transformed spi

      [Paragraph-level] PMCID: PMC2789045 Section: RESULTS PassageIndex: 3

      Evidence Type(s): Oncogenic, Functional

      Justification: Oncogenic: The passage discusses the ability of the FGFR3 mutations (S249C, Y375C, and K652E) to transform NIH-3T3 cells, indicating that these somatic variants contribute to tumor development or progression. Functional: The passage describes how the FGFR3 mutations alter molecular function, specifically through increased phosphorylation of various proteins and changes in cell morphology and proliferation, demonstrating their biochemical activity.

      Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

      Genes: 2261

      Variants: K652E S249C Y375C

      CIViC paragraph-level PMC2789045 Oncogenic Functional
    29. karim2001khoury 19 Feb 2026
      Although activating mutations of FGFR3 are frequent in bladder tumors, little information is available on their specific effects in urothelial cells or the basis for the observed mutation spectrum. We investigated the ph

      [Paragraph-level] PMCID: PMC2789045 Section: ABSTRACT PassageIndex: 1

      Evidence Type(s): Functional, Oncogenic

      Justification: Functional: The passage discusses how the FGFR3 mutations (S249C, Y375C, and K652E) alter molecular signaling pathways, specifically the phosphorylation of various proteins, indicating a change in biochemical function. Oncogenic: The passage describes how the mutant FGFR3 variants induce morphological transformation, cell proliferation, and anchorage-independent growth, which are indicative of their role in tumor development and progression.

      Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

      Genes: 2261

      Variants: K652E S249C Y375C

      CIViC paragraph-level PMC2789045 Functional Oncogenic
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    pmc.ncbi.nlm.nih.gov/articles/PMC2789045/pdf/ukmss-27839.pdf