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Molecular Biology, Pathobiology, and Genetics

Mouse Models for Xeroderma Pigmentosum Group A and Group C Show Divergent Cancer Phenotypes

Joost P.M. Melis, Susan W.P. Wijnhoven, Rudolf B. Beems, Marianne Roodbergen, Jolanda van den Berg, Hojin Moon, Errol Friedberg, Gijsbertus T.J. van der Horst, Jan H.J. Hoeijmakers, Jan Vijg and Harry van Steeg
Joost P.M. Melis
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Susan W.P. Wijnhoven
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Rudolf B. Beems
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Marianne Roodbergen
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Jolanda van den Berg
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Hojin Moon
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Errol Friedberg
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Gijsbertus T.J. van der Horst
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Jan H.J. Hoeijmakers
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Jan Vijg
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Harry van Steeg
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DOI: 10.1158/0008-5472.CAN-07-6067 Published March 2008
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    Figure 1.

    Survival curves of female Xpc−/−, Xpa−/− and their wild-type control cohorts. C57BL/6 1 is the control cohort for Xpa−/−. C57BL/6 2 is the control cohort for Xpc−/−. Median survival of the cohorts: C57BL/6 1, 103 wk (light green); C57BL/6 2, 102.5 wk (dark green); Xpc−/−, 94 wk (P = 0.0023; red); Xpa−/−, 94.5 wk (P = 0.6023; blue). For further details, see Materials and Methods.

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    Figure 2.

    Hprt mutant frequencies including SDs of Xpc−/−, Xpc+/− and their wild-type controls at ages 13 and 52 wk in spleen. The numbers of biological replicas are between 4 and 10. For further details, see Materials and Methods.

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    Figure 3.

    LacZ mutant frequencies including SDs of Xpc−/−, Xpa−/− and their wild-type controls at ages 13, 52, and 78 wk in spleen (A), liver (B), and lung (C). The numbers of biological replicas are between 5 and 6. For further details, see Materials and Methods.

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    Figure 4.

    Survival of MEFs including SDs of Xpc−/−, Xpa−/− and their wild-type controls under different levels of oxygen pressure. Cells at the first passage were all cultured in 3% oxygen (A); subsequent passages were cultured in 3% (B) or 20% (C) oxygen.

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  • Table 1.

    Tumor incidences and P values for difference between mutant and its wild-type group

    C57BL/6J 1Xpa−/−PC57BL/6J 2Xpc−/−P
    No. animals (absolute)40312938
    All organs
        Tumor-bearing animals30 (75)21 (68)24 (83)23 (61)
    Liver
        Hepatocellular tumor0 (0)3 (10)0.00022 (7)5 (13) *
    Lung
        Bronchioloalveolar tumor0 (0)2 (6)1 (3)6 (16)0.02
    Pituitary
        Pars distalis adenoma20 (50)8 (26) *20 (70)9 (24)0.01
    All organs
        Pituitary adenomas excluded18 (45)19 (61)0.00121 (72)23 (61) †
    • NOTE: Data are absolute values with percentages in brackets. Statistics: poly-k test (poly-3 test and Peto test generally gave similar significances, although exact P values may differ).

    • ↵* Approaches significance with poly-3 test only (P = 0.08 for Xpc−/− liver and P = 0.054 for Xpa−/− pituitary).

    • ↵† Not reaching significance with poly-k test, but P = 0.05 (positive trend) by the Peto test in this case.

  • Table 2.

    P values of mutant frequency comparisons between genotypes, depicted per age per tissue

    Spleen13 wk52 wk78 wkLiver13 wk52 wk78 wkLung13 wk52 wk78 wk
    Xpc vs WT0.0160.012Xpc vs WT0.002Xpc vs WT0.040.000030.0001
    Xpc vs Xpa0.00980.007Xpc vs XpaXpc vs Xpa0.020.0005
    Xpa vs WTXpa vs WT0.040.002Xpa vs WT0.0030.003
    • NOTE: Open cells represent nonsignificant (P > 0.05) differences.

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Cancer Research: 68 (5)
March 2008
Volume 68, Issue 5
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Mouse Models for Xeroderma Pigmentosum Group A and Group C Show Divergent Cancer Phenotypes
Joost P.M. Melis, Susan W.P. Wijnhoven, Rudolf B. Beems, Marianne Roodbergen, Jolanda van den Berg, Hojin Moon, Errol Friedberg, Gijsbertus T.J. van der Horst, Jan H.J. Hoeijmakers, Jan Vijg and Harry van Steeg
Cancer Res March 1 2008 (68) (5) 1347-1353; DOI: 10.1158/0008-5472.CAN-07-6067

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Mouse Models for Xeroderma Pigmentosum Group A and Group C Show Divergent Cancer Phenotypes
Joost P.M. Melis, Susan W.P. Wijnhoven, Rudolf B. Beems, Marianne Roodbergen, Jolanda van den Berg, Hojin Moon, Errol Friedberg, Gijsbertus T.J. van der Horst, Jan H.J. Hoeijmakers, Jan Vijg and Harry van Steeg
Cancer Res March 1 2008 (68) (5) 1347-1353; DOI: 10.1158/0008-5472.CAN-07-6067
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