RGD Reference Report - The Mcs7 quantitative trait locus is associated with an increased susceptibility to mammary cancer in congenic rats and an allele-specific imbalance. - Rat Genome Database

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The Mcs7 quantitative trait locus is associated with an increased susceptibility to mammary cancer in congenic rats and an allele-specific imbalance.

Authors: Cotroneo, MS  Merry, GM  Haag, JD  Lan, H  Shepel, LA  Gould, MN 
Citation: Cotroneo MS, etal., Oncogene. 2006 Aug 17;25(36):5011-7. Epub 2006 Mar 27.
RGD ID: 1581951
Pubmed: PMID:16568087   (View Abstract at PubMed)
DOI: DOI:10.1038/sj.onc.1209506   (Journal Full-text)

Identification of high-penetrance breast cancer genes such as Brca1 has been accomplished by analysing familial cases. However, these genes occur at low frequency and do not account for the majority of genetic risk. Identification of low-penetrance alleles that occur commonly in populations may benefit from unbiased genome-wide screening. One such approach uses linkage studies in rodent models to identify homologous human candidates. The Wistar Kyoto (WKy) rat is resistant to mammary carcinomas induced with 7,12-dimethybenz[a]anthracene (DMBA), whereas the Wistar Furth (WF) strain is susceptible. Previous genome-wide linkage studies in crosses of these strains identified three WKy resistance quantitative trait loci, Mcs5, Mcs6 and Mcs8, and one predicted to increase susceptibility, Mcs7. The Mcs7 region on rat chromosome 10 (RNO10) is orthologous to human 17q, a common site of genetic aberrations in breast cancer. Here, we establish the independent phenotype conferred by Mcs7 using congenic rats carrying the WKy Mcs7 locus on a WF background. Tumor multiplicity was significantly higher ( approximately 50%) in DMBA-treated congenics homozygous and heterozygous for the WKy allele at the Mcs7 locus, compared to controls. We also investigated allelic imbalance (AI) in mammary carcinomas from (WKy x WF)F1 rats and Mcs7 heterozygous congenics. Of the four known WKy Mcs loci tested, only Mcs7 displayed AI. The pattern of AI in carcinomas from both F1 and Mcs7 congenic rats was similar, suggesting a WF allelic loss. Together, these data suggest that one or more breast cancer-related genes are located within the dominantly acting WKy allele at the Mcs7 locus.



Disease Annotations    

Phenotype Annotations    

Mammalian Phenotype
Objects Annotated

QTLs
Mcs15  (Mammary carcinoma susceptibility QTL 15)
Mcs16  (Mammary carcinoma susceptibility QTL 16)
Mcs17  (Mammary carcinoma susceptibility QTL 17)
Mcs18  (Mammary carcinoma susceptibility QTL 18)
Mcs19  (Mammary carcinoma susceptibility QTL 19)
Mcs20  (Mammary carcinoma susceptibility QTL 20)
Mcs21  (Mammary carcinoma susceptibility QTL 21)
Mcs22  (Mammary carcinoma susceptibility QTL 22)

Objects referenced in this article
Strain WF/NHsd null Rattus norvegicus
Strain WKY/NHsd null Rattus norvegicus

Additional Information