Transduction and rearrangement of the myc gene by feline leukaemia virus in naturally occurring T-cell leukaemias

Neil, James C.; Hughes, David C.; McFarlane, Robert M.; Wilkie, N. M.; Onions, David; Lees, Gillian; Jarrett, Oswald

doi:10.1038/308814a0

Cited by 190 publications

(96 citation statements)

References 31 publications

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“…The disrupted chicken c-myc locus is often transcribed from a viral promoter present in the long terminal repeat (18,21,32) and sometimes from cryptic promoters (25,32). Murine thymomas caused by murine leukemia viruses as well as feline T-cell tumors caused by feline leukemia virus also frequently contain a disrupted c-myc locus (10,23,24,29,39). Chicken and feline c-myc genes are both progenitors of v-myc oncogenes contained in several replication-defective viruses and causing rapid onset of myelomonocytic tumors and carcinomas in chickens (1, 46) and lymphoid tumors in cats (23,29).…”

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confidence: 99%

“…Murine thymomas caused by murine leukemia viruses as well as feline T-cell tumors caused by feline leukemia virus also frequently contain a disrupted c-myc locus (10,23,24,29,39). Chicken and feline c-myc genes are both progenitors of v-myc oncogenes contained in several replication-defective viruses and causing rapid onset of myelomonocytic tumors and carcinomas in chickens (1, 46) and lymphoid tumors in cats (23,29). Although the function of the myc protein is speculative, the protein binds DNA in vitro (13,33), is associated with the nucleus in vivo (2,13,16,33), and may play a central role in the control of cell growth (8,22).…”

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confidence: 99%

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Features of the chicken c-myc gene that influence the structure of c-myc RNA in normal cells and bursal lymphomas.

Nottenburg¹,

Varmus²

1986

Mol. Cell. Biol.

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The chicken c-myc gene is the target for proviral insertion mutations in bursal lymphomas and has been transduced to generate several viral oncogenes, but the boundaries of its exons have not been securely established. To define the landmarks of the chicken c-myc gene necessary to produce its mRNA, we used an RNase protection assay and a cDNA clone to analyze the c-myc mRNAs from normal chicken embryos and from two bursal lymphomas: LL6, which contains an avian leukosis virus provirus downstream of the c-myc coding region, and LL7, which contains an avian leukosis virus provirus upstream of the c-myc coding region. Two initiation sites for normal c-myc mRNA are less than 7 bases apart, downstream of a GC-rich region lacking canonical TATA and CAAT sequences. The first exon has two open reading frames for the entire length but no initiator methionine codons. The splice donor and acceptor sites at the boundary of the first intron were assigned by comparing a sequence of an LL6 c-myc cDNA clone with a genomic DNA sequence and confirmed by RNase protection of labeled RNA probes by normal and LL6-derived mRNAs. Two potential polyadenylation signals are located approximately 250 and 400 bases downstream of the c-myc coding region in the third exon, but only the more distal signal is utilized in both normal cells and the LL7 tumor. The proviral integration in the LL6 tumor occurred upstream of the authentic c-myc polyadenylation signal accounting for polyadenylation of this transcript in the proviral long terminal repeat.

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confidence: 99%

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confidence: 99%

Features of the chicken c-myc gene that influence the structure of c-myc RNA in normal cells and bursal lymphomas.

Nottenburg¹,

Varmus²

1986

Mol. Cell. Biol.

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“…Although the steadystate levels of c-myc protein in exponentially growing cells are constant during the cell cycle {Hann et al 1985; Rabbitts et al 1985; Thompson et al 1985), decreased levels achieved by antisense c-myc oligonucleotides (Heikkila et al 1987) or by genetic disruption of one c-myc gene copy (Shichiri et al 1993) have been reported to interfere with cell growth, indicating that c-myc is required for cell-cycle progression. Moreover, constitutive overexpression of c-myc in some cell types reduces their growth factor requirement in vitro (Kaczmarek et al 1985) and predisposes to tumor formation in several experimental animal models (Corcoran et al 1984;Li et al 1984;Neil et al 1984;Selten et al 1984;Stewart et al 1984;Adams et al 1985;Leder et al 1986; Spanopoulou 6Corresponding author. et al 1989).…”

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confidence: 99%

Frequent provirus insertional mutagenesis of Notch1 in thymomas of MMTVD/myc transgenic mice suggests a collaboration of c-myc and Notch1 for oncogenesis.

Girard¹,

Hanna²,

Beaulieu³

et al. 1996

Genes Dev.

198

202

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The MMTVD/myc transgenic mice spontaneously develop oligoclonal CD4+CD8 + T-ceU tumors. We used provirus insertional mutagenesis in these mice to identify putative collaborators of c-myc. We found that Notchl was mutated in a high proportion (52%) of these tumors. Proviruses were inserted upstream of the exon coding for the transmembrane domain and in both transcriptional orientations. These mutations led to high expression of truncated Notchl RNAs and proteins (86-110 kD). In addition, many Notchl-rearranged tumors showed elevated levels of full-length Notchl transcripts, whereas nearly all showed increased levels of full-length (330-kD) or close to full-length (280-kD) Notchl proteins. The 5' end of the truncated RNAs were determined for some tumors by use of RT-PCR and 5' RACE techniques. Depending on the orientation of the proviruses, viral LTR or cryptic promoters appeared to be utilized, and coding potential began in most cases in the transmembrane domain. Pulse-chase experiments revealed that the 330-kD Notchl proteins were processed into 110-and 280-kD cleavage products. These results suggest that Notchl can be a frequent collaborator of c-myc for oncogenesis. Furthermore, our data indicate that Notchl alleles mutated by provirus insertion can lead to increased expression of truncated and full-length (330/280-kD) Notchl proteins, both being produced in a cleaved and uncleaved form.

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“…Similarly, erbB is specifically associated with erythroblastosis in chickens but with squamous cell carcinoma and other epithelial tumors in humans (3,10,14). By contrast, many more parallels exist with the myc oncogene whose activation has been linked to B-and T-cell disorders in a variety of species, including chicken, mouse, rat, cat, and human (2,9,16,25,29,34,37; reviewed in reference 30). It therefore remains an entirely open question whether int-2 will eventually be implicated in human tumors other than mammary carcinomas, and the negative findings to date in no way preclude further investigation along these lines.…”

Section: Discussionmentioning

confidence: 99%

Characterization and chromosome assignment of the human homolog of int-2, a potential proto-oncogene.

Casey¹,

Smith²,

McGillivray³

et al. 1986

Mol. Cell. Biol.

165

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int-2 is one of two cellular genes (int-i and int-2) currently implicated in the genesis of mammary carcinomas by mouse mammary tumor virus and may constitute a novel cellular proto-oncogene. Using low-stringency hybridization with mouse int-2 probes, we established that homologous genes exist in a variety of mammalian species, including humans, but failed to detect related sequences in other classes and phyla. Recombinant bacteriophage clones and a single cosmid encompassing the human int-2 gene were isolated and characterized by restriction enzyme mapping. A survey of nine primary human breast tumors, three breast tumor cell lines, and three normal individuals revealed no evidence for gross amplification or rearrangement of the int-2 locus. Three distinct restriction fragment length polymorphisms were observed which could prove useful in future linkage studies. By a combination of in situ hybridization of metaphase chromosomes and somatic cell genetics, the human int-2 gene was mapped to chromosome 11, band q13.

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Transduction and rearrangement of the myc gene by feline leukaemia virus in naturally occurring T-cell leukaemias

Abstract: Evidence of myc gene transduction by feline leukaemia virus in several spontaneous lymphoid tumours of cats suggests that recombinant viruses carrying oncogenes may be much more involved in oncogenesis in natural conditions than previously recognized.

Cited by 190 publications

References 31 publications

Features of the chicken c-myc gene that influence the structure of c-myc RNA in normal cells and bursal lymphomas.

Features of the chicken c-myc gene that influence the structure of c-myc RNA in normal cells and bursal lymphomas.

Frequent provirus insertional mutagenesis of Notch1 in thymomas of MMTVD/myc transgenic mice suggests a collaboration of c-myc and Notch1 for oncogenesis.

Characterization and chromosome assignment of the human homolog of int-2, a potential proto-oncogene.

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