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  • Oncogenomics
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Mapping of genetic modifiers of thymic lymphoma development in p53-knockout mice

Oncogene volume 22, pages 1098–1102 (2003)Cite this article

Abstract

The strain dependency of the spectrum and latency of tumors has been reported in p53-deficient (KO) mice, suggesting the presence of modifiers for the outcome of the p53 deficiency. The modifiers provide clues to the oncogenic pathway in cells lacking p53, the most frequently mutated gene in a wide variety of human cancers. To search the modifiers, we induced 160 lymphomas and 69 skin tumors by γ-irradiation of p53(KO/+) backcross mice between BALB/c and MSM strains and performed genome scan. BALB/c-derived alleles at three loci on chromosome 19, Mp53D1 (modifier of p53-deficiency) at D19Mit5, Mp53D2 at D19Mit90 and Mp53D3 at D19Mit123, extended the latency of thymic lymphoma development (P values in Mantel–Cox test were 0.0007, 0.0007 and 0.0003, respectively). Mp53D3 also increased the latency of skin tumors (P value, 0.0008). The linkage of Mp53D2 was confirmed by the experiment using 94 p53-KO mice consomic for chromosome 19, providing a significant linkage. However, the linkage was not confirmed for Mp53D1 or Mp53D3, suggesting epistasis of genes involved in the tumorigenesis.

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Acknowledgements

We thank Y. Saito for technical assistance and N Mori in Osaka Prefecture University for providing p53(KO/+) BALB/c. This work was supported by grants-in-aid of Second Term Comprehensive 10-year Strategy for Cancer Control from the Ministry of Health and Welfare of Japan.

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Authors and Affiliations

  1. Department of Gene Regulation, Graduate School of Medical and Dental Sciences, Niigata University, Asahimachi-doori 1-757, 951-8122, Niigata, Japan

    Yukie Ochiai, Yasushi Tamura, Yuko Saito, Atsushi Matsuki, Yu-ichi Wakabayashi & Ryo Kominami

  2. Department of Cardiovascular and Vital Control, Graduate School of Medical and Dental Sciences, Niigata University, Asahimachi-doori 1-757, 951-8122, Niigata, Japan

    Yukie Ochiai & Yoshifusa Aizawa

  3. Radiation Biology Center, Kyoto University, Yoshida-Konoecho, Sakyou-Ku, 606-8315, Kyoto, Japan

    Ohtsura Niwa

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  1. Yukie Ochiai
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Correspondence to Ryo Kominami.

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Ochiai, Y., Tamura, Y., Saito, Y. et al. Mapping of genetic modifiers of thymic lymphoma development in p53-knockout mice. Oncogene 22, 1098–1102 (2003). https://doi.org/10.1038/sj.onc.1206202

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