Recombination between two integrated proviruses, one of which was inserted near c-myc in a retrovirus-induced rat thymoma: implications for tumor progression.
Of 17 Moloney murine leukemia virus (MoMuLV)-induced rat thymomas, 2 contained rearrangements in c-myc. In one of these tumors the observed rearrangement was not due to the insertion of an intact MoMuLV provirus. The rearranged c-myc DNA fragment from this thymoma was cloned and examined by restriction endonuclease mapping, hybridization to MoMuLV proviral DNA probes, and DNA sequence analysis. These analyses revealed that the c-myc rearrangement in this tumor was due to the presence of a partially duplicated MoMuLV long terminal repeat (LTR) 5' to c-myc exon 1. The orientation of this LTR structure was opposite to the transcriptional orientation of c-myc. The sequences at the 3' flanking side of the LTR structure were derived from a cellular DNA region which maps to the same chromosome as c-myc (chromosome 7), although to a site distant from this proto-oncogene. These findings present evidence for a homologous recombination event occurring between sequences of two proviruses integrated on the same chromosome, one of which was inserted near the c-myc proto-oncogene. The recombination product contains three copies of the MoMuLV LTR 72-base-pair direct repeat and is associated with a high level of c-myc expression. The reciprocal product of this recombination was not detected. We propose that recombination between homologous sequences may play a significant role in the generation of chromosomal rearrangements and therefore in tumor induction and progression.
Lazo
P A
PA
Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111.
Tsichlis
P N
PN
D000818:Animals; D001483:Base Sequence; D004279:DNA, Viral / Q000032:analysis; D005786:Gene Expression Regulation; D005814:Genes, Viral; D008969:Molecular Sequence Data; D008979:Moloney murine leukemia virus / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc; D011519:Proto-Oncogenes; D011533:Proviruses / Q000235:genetics*; D051381:Rats; D011995:Recombination, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D012689:Sequence Homology, Nucleic Acid; D013945:Thymoma / Q000209:etiology / Q000235:genetics / Q000382:microbiology*; D013953:Thymus Neoplasms / Q000209:etiology / Q000235:genetics / Q000382:microbiology*
D004279:DNA, Viral; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc