Proviral deletions and oncogene base-substitutions in insertionally mutagenized c-myc alleles may contribute to the progression of avian bursal tumors.
Bursal lymphomas induced in chickens by avian leukosis viruses (ALVs) harbor proviral insertions that augment expression of an adjacent cellular oncogene, c-myc. To analyze such insertionally mutagenized c-myc genes in greater detail, we isolated molecular clones from two independent tumors. Precise proviral integration has occurred within the transcribed region of the c-myc gene in both mutant alleles. The proviruses bear different internal deletions that preclude the expression of the gag, pol, and env genes. The c-myc gene from bursal lymphoma LL4 contains a single copy of an ALV long terminal repeat (LTR), presumably the product of homologous recombination between LTRs at the ends of a normal provirus; the "solo" LTR is positioned in the correct orientation to act as a promoter for the c-myc gene. Bursal lymphoma LL3 contains an ALV provirus positioned upstream in the opposite transcriptional orientation to the coding exons of c-myc and deleted from a site within the leader region into the gag gene. In addition, the nucleotide sequence of the c-myc gene from tumor LL3 differs from the published sequence of the normal c-myc coding region at 3 positions of 180 determined. One of these changes, a silent nucleotide transition, is documented as a somatic mutation by restriction endonuclease mapping. It is flanked by two other candidate tumor-specific point mutations, one of which predicts an amino acid replacement, Pro----Thr at position 63. Thus, additional lesions that may affect the expression of viral genes and the quantity and nature of the putative c-myc gene product occur in provirally mutated c-myc alleles and may contribute to tumor progression.
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001354:Avian Leukosis Virus / Q000235:genetics*; D001358:Avian Sarcoma Viruses / Q000235:genetics; D001483:Base Sequence; D002645:Chickens; D002872:Chromosome Deletion; D003001:Cloning, Molecular; D004262:DNA Restriction Enzymes; D005814:Genes, Viral; D009154:Mutation; D009693:Nucleic Acid Hybridization; D009857:Oncogenes
D004262:DNA Restriction Enzymes