Nonrandom duplication of the chromosome bearing a mutated Ha-ras-1 allele in mouse skin tumors.
We analyzed the normal/mutated allelic ratio of the Ha-ras-1 gene in mouse skin squamous cell carcinomas induced by initiation with dimethylbenz[a]anthracene and promotion with phorbol 12-myristate 13-acetate. DNA for these studies was obtained from short-term tumor cultures (24-72 hr) to eliminate the contribution of stromal and inflammatory cells to the sample. The allelotypic analysis was performed in 25 squamous cell carcinomas by quantitative radio-analysis of the Xba I restriction fragment length polymorphism as detected by BS9, a v-Ha-ras probe, and rehybridization of the Southern blots with probes for chromosomes 7 and 8. Approximately 85% of the tumors presented overrepresentation of the mutated allele in the form of 1 normal/2 mutated (12 tumors), 0 normal/3 mutated (4 tumors), 0 normal/2 mutated (3 tumors), and gene amplification (3 tumors). No tumor was found with a 2 normal/1 mutated allelic ratio. These results support our previous cytogenetic studies, indicating that trisomy of chromosome 7 is present in the majority of these tumors and show that nonrandom duplication of the chromosome carrying the mutated Ha-ras-1 allele appears to be a major mechanism by which the mutated gene is overrepresented.
Department of Carcinogenesis, University of Texas, M.D. Anderson Cancer Center, Smithville 78957.
A B
AB
Bianchi
C M
CM
Aldaz
C J
CJ
Conti
D015127:9,10-Dimethyl-1,2-benzanthracene; D000483:Alleles; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D002454:Cell Differentiation; D002471:Cell Transformation, Neoplastic; D002874:Chromosome Mapping; D005784:Gene Amplification; D011905:Genes, ras; D007124:Immunoenzyme Techniques; D007633:Keratins / Q000032:analysis; D051379:Mice; D008815:Mice, Inbred Strains; D008957:Models, Genetic; D009154:Mutation; D009693:Nucleic Acid Hybridization; D012150:Polymorphism, Restriction Fragment Length; D012878:Skin Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology
D015127:9,10-Dimethyl-1,2-benzanthracene; D007633:Keratins