ArticleProceedings of the National Academy of Sciences of the United States of America1991
Overlapping loss of heterozygosity by mitotic recombination on mouse chromosome 7F1-ter in skin carcinogenesis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1991. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 38 citations in OpenAlex.
- Mathematical modeling of noise and discovery of genetic expression classes in gliomas.Oncogene · 2002Article
- Mouse mammary tumor virus/v-Ha-ras transgene-induced mammary tumors exhibit strain-specific allelic loss on mouse chromosome 4.Proceedings of the National Academy of Sciences of the United States of America · 1997Article
- Phenotypic reversions at the W/Kit locus mediated by mitotic recombination in mice.Molecular and cellular biology · 1995Article
- Unequal homologous recombination of human DNA on a yeast artificial chromosome.Nucleic acids research · 1995Article
- (C-A)n microsatellite repeat D7S522 is the most commonly deleted region in human primary breast cancer.Proceedings of the National Academy of Sciences of the United States of America · 1994Article
- Allelotyping of butadiene-induced lung and mammary adenocarcinomas of B6C3F1 mice: frequent losses of heterozygosity in regions homologous to human tumor-suppressor genes.Proceedings of the National Academy of Sciences of the United States of America · 1994Article
- Benzo[a]pyrene-induced murine skin tumors exhibit frequent and characteristic G to T mutations in the p53 gene.Proceedings of the National Academy of Sciences of the United States of America · 1993Article
- Reassignment of the H-ras-1 gene to the Hbb-terminus region of mouse chromosome 7.Mammalian genome : official journal of the International Mammalian Genome Society · 1993Article
- Mouse chromosome 7.Mammalian genome : official journal of the International Mammalian Genome Society · 1992Review
- A novel polymorphism near the mouse Int-2 locus.Mammalian genome : official journal of the International Mammalian Genome Society · 1992Article
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Authors and funding
4 authors at 1 institution in 1 country.
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Abstract
A significant role for mouse chromosome 7 abnormalities during chemically induced skin carcinogenesis has been advanced based on previous cytogenetic and molecular studies. To determine the frequency of allelic losses at different loci of chromosome 7 in skin tumors induced in the outbred SENCAR mouse stock by a two-stage initiation-promotion protocol, we compared the constitutional and tumor genotypes of premalignant papillomas and squamous cell carcinomas for loss of heterozygosity at different informative loci. In a previous study, these tumors had been analyzed for their allelic composition at the Harvey ras-1 (Ha-ras-1) locus and it was found that 39% of squamous cell carcinomas had lost the normal Ha-ras-1 allele exhibiting 3 or 2 copies of the mutated counterpart or gene amplification. In the present study, by combining Southern blot and polymerase chain reaction fragment length polymorphism analyses, we detected complete loss of heterozygosity at the beta-globin (Hbb) locus, distal to Ha-ras-1, in 15 of 20 (75%) skin carcinomas. In addition, 5 of 5 informative cases attained homozygosity at the int-2 locus, 27 centimorgans distal to Hbb. Polymerase chain reaction analysis of DNA extracted from papillomas devoid of stromal contamination by fluorescence-activated sorting of single cell dispersions immunolabeled with anti-keratin 13 antibody revealed loss of heterozygosity at the Hbb locus, demonstrating that this event occurs during premalignant stages of tumor development. Interestingly, loss of heterozygosity was only detected in late-stage lesions exhibiting a high degree of dysplasia and areas of microinvasion. Analysis of allelic ratios by densitometric scanning of tumors that had become homozygous at Hbb but retained heterozygosis at Ha-ras-1 indicated mitotic recombination as the mechanism underlying loss of heterozygosity on mouse chromosome 7 during chemically induced skin carcinogenesis. These findings are consistent with the presence of a putative tumor suppressor gene linked to the Hbb locus in the 7F1-ter region of mouse chromosome 7, the functional inactivation of which may constitute a critical event in skin tumor progression, possibly during the malignant conversion stage.
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