RGD Reference Report - Loss of heterozygosity at the N-ras locus in 7,12-dimethylbenz anthracene-induced rat leukemia. - Rat Genome Database

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Loss of heterozygosity at the N-ras locus in 7,12-dimethylbenz anthracene-induced rat leukemia.

Authors: Osaka, M  Matsuo, S  Koh, T  Sugiyama, T 
Citation: Osaka M, etal., Mol Carcinog. 1997 Apr;18(4):206-12.
RGD ID: 11535063
Pubmed: (View Article at PubMed) PMID:9142215

The 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat leukemia model enables scientists to analyze cells altered by carcinogens at various stages of leukemogenesis. We have reported that a consistent type of point mutation. A-->T transversion at the second base in codon 61 of the N-ras gene, was present in this leukemia and that this mutation appeared in bone marrow cells as early as 48 h after a single dose of DMBA. In addition, two leukemia cell lines with the N-ras mutation had no wild-type N-ras allele. Therefore, we examined whether these alterations were essential to the DMBA-induced leukemias. In the study reported here, we confirmed the occurrence of this N-ras mutation in 18 (86%) of 21 primary leukemias and loss of the N-ras wild-type allele in 12 (67%) of 18 leukemias with the mutated N-ras. By using microsatellite markers on chromosome 2, loss of heterozygosity (LOH) at the N-ras locus was observed in eight leukemias, all of which were shown to have lost the wild-type N-ras allele by mutant-allele-specific amplification. These results suggest that LOH related to loss of the wild-type N-ras allele reproducibly occurs in leukemias with the N-ras mutation. Considering the timing of the N-ras mutation and LOH, it is likely that the N-ras mutation is induced early, and cells that have lost the wild-type N-ras allele seem to develop into leukemia. We believe that this system provides a suitable model for studying a series of genetic alterations from the earliest stage of carcinogenesis that cannot be approached in human malignancies.

Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Nras  (NRAS proto-oncogene, GTPase)

Genes (Mus musculus)
Nras  (neuroblastoma ras oncogene)

Genes (Homo sapiens)
NRAS  (NRAS proto-oncogene, GTPase)

Additional Information