Experiment
86 microsatellite markers at an average spacing of 20 cM (approximately 74% genome coverage) were screened in 62 mammary carcinomas from (BALB/c x C57BL/6)F1 MMTV/neu trangenic female mice to identify loci involved in mammary tumor formation. Several loci designated Naad (Neu associated allelic deletion) were identified on mouse Chromosomes 4, 19, and 8 in association with loss of heterozygosity (LOH) and/or allelic imbalance (AI). On mouse Chromosome 4, Naad1 is associated with 28% LOH at D4Mit236 (12.1cM), Naad2 is associate with 32% LOH at D4Mit111 (21.9 cM), Naad3 is associated with 42 % LOH at D4Mit178 (35.5 cM), Naad4 is associated with 37% LOH at D4Mit12 (57.6 cM), and Naad5 is associated with 58% LOH at D4Mit54 (66 cM). Preferential loss of BALB/c alleles is observed at these loci, Naad1-Naad5 (21/30 mammary tumors). Naad3 maps near 2 candidate tumor suppressor genes, Cdkn2a and Cdkn2b, and colocalizes with a thymic lymphoma suppression QTL, Tlsr1 (Santos et al, J:31797). Naad4 maps near Lci (liver cell immortalization-Lee et al, J:30263) at 57.5 cM. Naad5 maps near possible candidate gene Plag2a (Mom1) and colocalizes with a thymic lymphoma suppression QTL, Tlsr2 (Santos et al, J:31797). On mouse Chromosome 19, Naad6 is associated with 24%-26% LOH at D19Mit19 and D19Mit10 (26 cM - 47 cM) and Naad7 is associated with 26% LOH at D19Mit34 (53 cM). Preferential loss of C57BL/6 alleles is observed at Naad6 and Naad7 (15/20 mammary tumors). Naad6 maps near Pten (phosphatase and tensin homolog) and colocalizes with Pas3, a pulomonary adenoma susceptibility QTL. On mouse Chromosome 8, Naad8 is associated with 18% LOH at D8Mit86 (52 cM) and maps near the E-cadherin gene, Cdh1. Naad9 is associated with 21% LOH at D8Mit91 (67 cM) and maps near candidate tumor suppressor genes Aprt and Cdh15.
Analysis Tools