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Susceptibility to testicular germ-cell tumours in a 129.MOLF-Chr 19 chromosome substitution strain

Nature Genetics volume 23, pages 237–240 (1999)Cite this article

Abstract

The identification of genes that control susceptibility to testicular germ-cell tumours (TGCTs), the most common cancer affecting young men1, has been difficult. In laboratory mice, TGCTs arise from primordial germ cells2,3 in only the 129 inbred strains4, and susceptibility is under multigenic control. The spontaneously arising mutation Ter (ref. 5) on mouse chromosome 18 (Refs 6,7) increases TGCT frequency5,8 on a 129/Sv background. We originally used Ter in genetic crosses to identify loci that control tumorigenesis. A genome scan of tumour-bearing progeny from backcrosses between the 129/Sv-Ter/+ and MOLF/Ei strains provided modest evidence that MOLF-derived alleles on chromosome 19 enhance development of bilateral TGCTs (ref. 9). To obtain independent evidence for linkage to the MOLF chromosome, we made an autosomal chromosome substitution strain (CSS; or 'consomic strain') in which chromosome 19 of 129/Sv+/+ was replaced by its MOLF-derived homologue. The unusually high frequency of TGCTs in this CSS (even in the absence of the Ter mutation) provides evidence confirming the genome survey results, identifies linkage for a naturally occurring strain variant allele that confers susceptibility to TGCTs and illustrates the power of CSSs in complex trait analysis.

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Figure 1: Histology of TGCT from a 129.
Figure 2: Location of the susceptibility locus on chromosome 19.
Figure 3: Partitioned-χ2 values from the G-test for heterogeneity for genotypes of normal F2 males (a), all tumour-bearing F2 males (b), males with unilateral tumours (c) and males with bilateral tumours (d).

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Acknowledgements

We thank K. Youngren and T. Nelson for expert technical assistance; P. Hunt for critical reading of the manuscript; R. Redline and M.-A. Handel for assistance with histology; and X. Montagutelli for helpful suggestions regarding the genetic analysis. This work was supported by NCI grant CA75056 and by a grant from the Howard Hughes Medical Institute to Case Western Reserve University School of Medicine.

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Authors and Affiliations

  1. Department of Genetics, Case Western Reserve University School of Medicine, and Center for Human Genetics & Ireland Cancer Center, University Hospitals of Cleveland, Cleveland, 44106-4955, Ohio, USA

    Angabin Matin & Joseph H. Nadeau

  2. The Jackson Laboratory, Bar Harbor, 04609, Maine, USA

    Gayle B. Collin & Don Varnum

  3. Department of Pedodontics, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba, Japan

    Yoshinobu Asada

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  1. Angabin Matin
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  4. Don Varnum
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  5. Joseph H. Nadeau
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Correspondence to Joseph H. Nadeau.

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Matin, A., Collin, G., Asada, Y. et al. Susceptibility to testicular germ-cell tumours in a 129.MOLF-Chr 19 chromosome substitution strain. Nat Genet 23, 237–240 (1999). https://doi.org/10.1038/13874

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