Mammary tumor modifiers in BALB/cJ mice heterozygous for p53.
BALB/c mice are predisposed to developing spontaneous mammary tumors, which are further increased in a p53 heterozygous state. C57BL/6J mice are resistant to induced mammary tumors and develop less than 1% mammary tumors in both wild-type and p53+/- states. To map modifiers of mammary tumorigenesis, we have established F1 and F2 crosses and backcrosses to BALB/cJ (N2-BALB/cJ) and C57BL/6J (N2-C57BL/6J) strains. All cohorts developed mammary carcinomas in p53+/- females, suggesting that multiple loci dominantly and recessively contributed to mammary tumorigenesis. We mapped two modifiers of mammary tumorigenesis in the BALB/cJ strain. Mtsm1 (mammary tumor susceptibility modifier), a dominant-acting modifier, is located on chromosome 7. Mtsm1 is suggestive for linkage to mammary tumorigenesis (p = 0.001). We have analyzed the Mtsm1 region to locate candidate genes by comparing it to a rat modifier region, Mcs3, which shares syntenic conservation with Mtsm1. Expression data and SNPs were also taken into account. Five potential candidate genes within Mtsm1 are Aldh1a3, Chd2, Nipa2, Pcsk6, and Tubgcp5. The second modifier mapped is Mtsm2, a recessive-acting modifier. Mtsm2 is located on chromosome X and is significantly linked to mammary tumorigenesis (p = 1.03 x 10(-7)).
Koch
Joanna G
JG
The University of Texas Graduate School of Biomedical Sciences and the Department of Cancer Genetics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Gu
Xiangjun
X
Han
Younghun
Y
El-Naggar
Adel K
AK
Olson
Melissa V
MV
Medina
Daniel
D
Jerry
D Joseph
DJ
Blackburn
Anneke C
AC
Peltz
Gary
G
Amos
Christopher I
CI
Lozano
Guillermina
G
D000818:Animals; D003433:Crosses, Genetic; D005260:Female; D016158:Genes, p53; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D008297:Male; D015674:Mammary Neoplasms, Animal / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D051381:Rats; D013047:Specific Pathogen-Free Organisms