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Genetic mapping of a pulmonary adenoma resistance locus (Par1) in mouse

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Abstract

Lung cancer, a major cause of death in the Western world, has a poor prognosis1. So far, therapeutic strategies have had only a limited effect. Lung cancer risk is strongly associated with cigarette smoking2,3 and lung cancer pedigrees are rare. However, a possible polygenic nature of inherited predisposition to this cancer has been envisaged4–7. Mouse inbred strains with inherited predisposition and resistance to lung cancer provide an important tool for the dissection of the genetics of this complex disease7,8. The A/J strain carries the pulmonary adenoma susceptibility 1 (Pas7) locus and develops many lung tumours9. We have mapped the M. spretus-derived locus that strongly resists the lung tumorigenesis in Pas1/+ mice. This locus, pulmonary adenoma resistance 1 (Par1) maps to mouse chromosome 11, near the Rara locus, with a lod score of 5.3. In Pas1/+ mice Par1 accounts for 23% of the phenotypic variance and 10 fold reduction in total tumour volume. These results provide evidence for a major resistance locus affecting the expression of an inherited predisposition to lung cancer.

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Authors and Affiliations

  1. Division of Experimental Oncology A, Istituto Nazionale Tumori, Via G. Venezian 1, 20133, Milan, Italy

    Giacomo Manenti, Manuela Gariboldi, Antonio Fiorino, Laura De Gregorio, F. Stefania Falvella, Marco A. Pierotti & Tommaso A. Dragani

  2. Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, 02139, USA

    Ramu Elango, Kent Hunter & David Housman

Authors
  1. Giacomo Manenti
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  2. Manuela Gariboldi
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  3. Ramu Elango
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  4. Antonio Fiorino
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  5. Laura De Gregorio
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  6. F. Stefania Falvella
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  7. Kent Hunter
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  8. David Housman
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  9. Marco A. Pierotti
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  10. Tommaso A. Dragani
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Manenti, G., Gariboldi, M., Elango, R. et al. Genetic mapping of a pulmonary adenoma resistance locus (Par1) in mouse. Nat Genet 12, 455–457 (1996). https://doi.org/10.1038/ng0496-455

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  • DOI: https://doi.org/10.1038/ng0496-455

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