title: Predisposition to efficient mammary tumor metastatic progression is linked to the breast cancer metastasis suppressor gene Brms1.
abstract: Tumor metastasis is one of the most important clinical aspects of neoplastic disease because patient mortality is frequently attributable to disseminated rather than primary tumors. However, it still is not possible to definitively distinguish those individuals at high risk for disseminated disease, who would benefit from aggressive adjuvant therapy, from the low-risk patients who might be spared the side effects of additional anticancer therapy. To identify factors that predispose toward metastatic disease, we have used a genetic approach. Using a highly metastatic model of mammary cancer, we identified previously inbred mouse strains (DBA/2J, NZB/B1NJ, and I/LnJ) that harbor genetic factors that significantly suppress metastatic efficiency. In this study, we report the results of four experiments to localize the genetic map locations of the metastasis efficiency modifier genes. One statistically significant locus was identified on proximal Chr 19 designated Mtes1. Secondary candidate intervals were detected on Chrs 6, 9, 13, and 17. Interestingly, Mtes1 colocalizes with the murine orthologue of the human breast cancer metastasis suppressor gene Brms1, suggesting that allelic variants of Brms1 might be responsible for the metastasis suppression observed.
authors.affiliation: Laboratory of Population Genetics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Hunterk@mail.nih.gov
authors.forename: K W
authors.initials: KW
authors.lastname: Hunter
authors.forename: K W
authors.initials: KW
authors.lastname: Broman
authors.forename: T L
authors.initials: TL
authors.lastname: Voyer
authors.forename: L
authors.initials: L
authors.lastname: Lukes
authors.forename: D
authors.initials: D
authors.lastname: Cozma
authors.forename: M T
authors.initials: MT
authors.lastname: Debies
authors.forename: J
authors.initials: J
authors.lastname: Rouse
authors.forename: D R
authors.initials: DR
authors.lastname: Welch
mesh_terms: D000818:Animals; D005260:Female; D016147:Genes, Tumor Suppressor; D020022:Genetic Predisposition to Disease; D007178:Inbreeding; D008175:Lung Neoplasms / Q000235:genetics / Q000556:secondary*; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000235:genetics* / Q000473:pathology*; D051379:Mice; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins; D011506:Proteins / Q000235:genetics*; D012097:Repressor Proteins
chemical_list: C410024:BRMS1 protein, human; D009363:Neoplasm Proteins; D011506:Proteins; D012097:Repressor Proteins