title: Identification of Stmm3 locus conferring resistance to late-stage chemically induced skin papillomas on mouse chromosome 4 by congenic mapping and allele-specific alteration analysis.
abstract: Genome-wide association studies have revealed that many low-penetrance cancer susceptibility loci are located throughout the genome; however, a very limited number of genes have been identified so far. Using a forward genetics approach to map such loci in a mouse skin cancer model, we previously identified strong genetic loci conferring resistance to chemically induced skin papillomas on chromosome 4 and 7 with a large number of [(FVB/N × MSM/Ms) F₁ × FVB/N] backcross mice. In this report, we describe a combination of congenic mapping and allele-specific alteration analysis of the loci on chromosome 4. We used linkage analysis and a congenic mouse strain, FVB.MSM-Stmm3 to refine the location of Stmm3 (Skin tumor modifier of MSM 3) locus within a physical interval of about 34 Mb on distal chromosome 4. In addition, we used patterns of allele-specific imbalances in tumors from N₂ and N₁₀ congenic mice to narrow down further the region of Stmm3 locus to a physical distance of about 25 Mb. Furthermore, immunohistochemical analysis showed papillomas from congenic mice had less proliferative activity. These results suggest that Stmm3 responsible genes may have an influence on papilloma formation in the two-stage skin carcinogenesis by regulating papilloma growth rather than development.
authors: Department of Carcinogenesis Research, Division of Experimental Animal Research, Chiba Cancer Center Research Institute, 666-2 Nitonacho, Chuouku, Chiba 260-8717, Japan.
authors: Megumi
authors: M
authors: Saito
authors: Kazuhiro
authors: K
authors: Okumura
authors: Ikuo
authors: I
authors: Miura
authors: Shigeharu
authors: S
authors: Wakana
authors: Ryo
authors: R
authors: Kominami
authors: Yuichi
authors: Y
authors: Wakabayashi
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D033481:Chromosomes, Mammalian / Q000235:genetics*; D056426:Genetic Loci / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D020297:Mice, Congenic; D008815:Mice, Inbred Strains; D009367:Neoplasm Staging; D010212:Papilloma / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000235:genetics* / Q000473:pathology