title: Proviral deletions and oncogene base-substitutions in insertionally mutagenized c-myc alleles may contribute to the progression of avian bursal tumors.
abstract: 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.
mesh_terms: 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
chemical_list: D004262:DNA Restriction Enzymes