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

EMBO J. 1986 Feb;5(2):301-9.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Avian Leukosis Virus / genetics*
  • Avian Myeloblastosis Virus / genetics*
  • Base Sequence
  • Chickens
  • Cloning, Molecular
  • DNA / analysis
  • DNA Restriction Enzymes
  • Genes, Viral*
  • Lymphoma / microbiology
  • Mice
  • Oncogenes*
  • RNA, Neoplasm / genetics
  • RNA, Viral / genetics
  • Transcription, Genetic
  • Wilms Tumor / microbiology*

Substances

  • RNA, Neoplasm
  • RNA, Viral
  • DNA
  • DNA Restriction Enzymes

Associated data

  • GENBANK/X03578