RESUMEN
The 5.2-kilobase (kb) RNA genome of avian carcinoma virus MH2 has the genetic structure 5' - delta gag (0.2 kb)-mht (1.2 kb)-myc (1.4 kb)-c(0.4 kb)-poly (A) (0.2 kb)-3'. delta gag is a partial retroviral core protein, mht and myc are cell-derived MH2-specific sequences, and c is the 3'-terminal retroviral vector sequence. the following results were obtained from the complete nucleotide sequences of the mht and myc genes in MH2. (i) delta gag-mht forms a hybrid gene with a contiguous reading frame of 2682 nucleotides that terminates with a stop codon near the 3' end of the mht gene. The 3' 969 nucleotides of mht up to the stop codon are 80% sequence related to the onc-specific raf sequence of murine sarcoma virus 3611 (MSV 3611) (94% homologous at the deduced amino acid level). (ii) The myc coding region in MH2 is preceded by 181 nucleotides derived from the intron immediately upstream from the second exon of the chicken cellular proto-myc gene, followed by an RNA splice acceptor site shared with the proto-myc gene, followed by an RNA splice acceptor site shared with the proto-myc, beyond which it is colinear up to a 3'-termination codon and 40 noncoding nucleotides with the myc sequences of avian retrovirus MC29 and chicken proto-myc. Thus, myc forms, together with a 5' retroviral exon, a second MH2-specific gene. It is concluded that MH2 contains two genes with oncogenic potential, the delta gag-mht gene, which is closely related to the delta gag-raf transforming gene of MSV 3611, and the myc gene, which is related to the transforming gene of MC29. Furthermore, it may be concluded that the cellular proto-onc genes, which on sequence transduction become viral onc genes, are a small group because among the 19 known onc sequences, 5 are shared by different taxonomic groups of viruses of which the mht/raf homology is the closest so far.
Asunto(s)
Oncogenes , Retroviridae/genética , Alpharetrovirus/genética , Animales , Secuencia de Bases , Pollos/genética , Mapeo Cromosómico , Clonación Molecular , Codón , Humanos , Especificidad de la EspecieAsunto(s)
Virus de la Leucosis Aviar/genética , Genes , Oncogenes , Animales , Virus de la Mieloblastosis Aviar/genética , Secuencia de Bases , Pollos , Clonación Molecular , Enzimas de Restricción del ADN , Humanos , Hibridación de Ácido Nucleico , Especificidad de la Especie , Transducción GenéticaRESUMEN
c-myc is the cellular gene homologous to the transforming sequence of MC29, an acute avian retrovirus. The human c-myc gene was cloned and used to study the structure and expression of c-myc in a variety of human hematopoietic malignancies. In a careful study of 106 patients, c-myc RNA was found to be expressed at elevated levels in tumor cells of 17 leukemia patients and five lymphoma patients. The c-myc gene was found to be rearranged in two lymphomas, an African Burkitt's lymphoma and a non-Hodgkins lymphoma in leukemic phase. The Burkitt's rearrangement involved the insertion of new DNA sequences upstream from the c-myc 5' coding region, presumably replacing the normal c-myc transcriptional promoter. None of the other 104 patients, including 20 with elevated myc expression, exhibited any evidence of a genetic rearrangement involving the c-myc gene. Our results show that there is a subset of hematopoietic malignancies characterized by elevated expression of c-myc. This elevated expression in most cases is not due to obvious genetic changes (rearrangement, amplification) at the c-myc locus nor to chromosomal translocations in the vicinity of this gene.