Send to

Choose Destination
Oncol Lett. 2018 Nov;16(5):6670-6676. doi: 10.3892/ol.2018.9495. Epub 2018 Sep 24.

Mapping of new skin tumor susceptibility loci by a phenotype-driven congenic approach.

Author information

Division of General Medicine, Department of Medicine, Nihon University School of Medicine, Tokyo 173-0032, Japan.
Department of Internal Medicine, Sasaki Foundation Kyoundo Hospital, Tokyo 101-0062, Japan.
Laboratory of DNA Damage Signaling, Chiba Cancer Center Research Institute, Chiba 260-8717, Japan.
Laboratory of Cancer Genetics, Chiba Cancer Center Research Institute, Chiba 260-8717, Japan.


As cancer susceptibility varies among mouse strains, mouse models are powerful tools for the identification of genes responsible for cancer development. Several cancer susceptibility loci have been mapped by genetic analysis using cancer-resistant and cancer-susceptible mouse strains. However, only a few corresponding genes for these loci have been identified, because most of the cancer susceptibility loci are low-penetrance alleles. We reported previously that wild-derived PWK mice showed no tumor development on treatment with the two-stage skin carcinogenesis protocol [induced by 7.12-dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)], and that this phenotype is dominant-resistant when crossed with the highly susceptible strain FVB. From the analysis of the F1 backcross generation between PWK and FVB, we have mapped the new significant locus Skts-fp1 on chromosome 4. In the present study, congenic strains were generated with the PWK resistance allele in the FVB background using a phenotype-driven approach, and sought to narrow down the candidate loci and find the responsible gene(s). One of the resistant mice in the N6 generation carried the remaining PWK allele on chromosomes 4, 7 and 11, and an association study using the progeny of this mouse suggested that the locus on chromosome 11 may affect the cancer susceptibility locus on chromosome 7. On the other hand, no skin tumor susceptibility locus was mapped on chromosome 11 as examined in N2 progeny. These findings suggest that there is at least one tumor-resistance gene on chromosome 7, the function of which could be regulated by gene(s) located on chromosome 11.


cancer susceptibility; mouse model; squamous cell carcinoma; two stage skin carcinogenesis

Supplemental Content

Full text links

Icon for PubMed Central
Loading ...
Support Center