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Identification of a provirally activated c‐Ha‐ras oncogene in an avian nephroblastoma via a novel procedure: cDNA cloning of a chimaeric viral‐host transcript.
Author(s) -
Westaway D.,
Papkoff J.,
Moscovici C.,
Varmus H.E.
Publication year - 1986
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/j.1460-2075.1986.tb04213.x
Subject(s) - biology , complementary dna , retrovirus , cloning (programming) , messenger rna , genetics , cdna library , gene , microbiology and biotechnology , expressed sequence tag , virology , computer science , programming language
Retrovirus without oncogenes often exert their neoplastic potential as insertional mutagens of cellular proto‐oncogenes. This may be associated with the production of chimaeric viral‐host transcripts; in these cases; activated cellular genes can be identified by obtaining cDNA clones of bipartite RNAs. This approach was used in the analysis of chicken nephroblastomas induced by myeloblastosis‐associated virus (MAV). One tumor contained a novel mRNA species initiated within a MAV LTR. cDNA cloning revealed that this mRNA encodes a protein of 189 amino acids, identical to that of normal human Ha‐ras‐1 at 185 positions, including positions implicated in oncogenic activation of ras proto‐oncogenes; there are no differences between the coding sequences of presumably normal Ha‐ras cDNA clones from chicken lymphoma RNA and the tumor‐derived cDNAs. The chimaeric mRNA in the nephroblastoma is at least 25‐fold more abundant than c‐Ha‐ras mRNA in normal kidney tissue, and a 21‐kd ras‐related protein is present in relatively large amounts in the tumor. We conclude that a quantitative change in c‐Ha‐ras gene expression results from an upstream insertion mutation and presumably contributes to tumorigenesis in this single case. Little or no increase in c‐Ha‐ras RNA or protein was observed in other nephroblastomas.