ACTIVATION OF THE K-RAS GENE BY INSERTION MUTATIONS IN CHEMICALLY-INDUCED RAT RENAL MESENCHYMAL TUMORS

Citation
Kg. Higinbotham et al., ACTIVATION OF THE K-RAS GENE BY INSERTION MUTATIONS IN CHEMICALLY-INDUCED RAT RENAL MESENCHYMAL TUMORS, Oncogene, 9(9), 1994, pp. 2455-2459
Citations number
30
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Genetics & Heredity",Oncology
Journal title
ISSN journal
0950-9232
Volume
9
Issue
9
Year of publication
1994
Pages
2455 - 2459
Database
ISI
SICI code
0950-9232(1994)9:9<2455:AOTKGB>2.0.ZU;2-6
Abstract
Previously we reported the detection of transforming K-ras sequences i n methyl(methoxymethyl)nitrosamine (DMN-OMe)-induced rat renal mesench ymal tumors by NIH3T3 transfection assays. Subsequent analysis by sele ctive oligonucleotide hybridization revealed a variety of activating p oint mutations in codon 12 of K-ras in most of these tumors and in the ir NIH3T3 transformants, but in some, point mutations could not be det ected by this technique. In the current study, insertion mutations wer e detected in two DMN-OMe-induced tumors from this group with previous ly undefined transforming K-ras alterations. These primary tumors and their NIH3T3 transformants contained K-ras sequences with either a 9 b p or a 12 bp repeat in exon one, both of which included codon 12. No o ther mutations in the entire coding region of the K-ras gene were obse rved. Site-directed mutagenesis studies by others have determined that deletions and insertions near codon 12 can activate the ras gene, but this is the first demonstration of insertional activation of K-ras in a chemically induced rat tumor.