Ecotropic and mink cell focus-forming murine leukemia viruses integrate in mouse T, B, and non-T/non-B cell lymphoma DNA (original) (raw)
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Cell, 1984
A number of mink cell focus-forming (MCF) proviruses was molecularly cloned from mouse lymphoma DNA. From each clone, flanking probes were prepared to detect common integration regions in other MuLV-induced lymphomas. One clone frequently revealed variations in the molecular structure of the corresponding region (Pim-1) in other lymphomas. The results show the following. Changes in the Pim region are seen in 24 out of 93 lymphomas tested. Over 50% of the early T-cell lymphomas show integration in the Pim-1 region. The alterations are seen in different mouse strains and with various MuLVs. The observed variations are caused by the integration of predominantly MCF genomes. All integrations occur in a region spanning less than 20 kb and are associated with the transcriptional activation of a distinct region within the Pim-1 domain. The activated region does not show any homology with 13 known and three putative oncogenes.
Journal of Virology, 1984
We studied the appearance and structure of murine leukemia viral genomes in preleukemic AKR/J mice by Southern hybridization. Up to an average of one to two copies per thymocyte of unintegrated murine leukemia virus DNA appears in the thymuses of preleukemic mice beginning at 4 to 5 months of age and disappears in leukemic thymuses. The free viral genomes are absent in the spleens, livers, and brains of preleukemic mice. Using a series of ecotropic and nonecotropic murine leukemia virus hybridization probes, we showed that the unintegrated viral genomes are structurally analogous to those of recombinant mink cell focus-forming viruses that appear as proviruses in leukemic AKR thymocytes, suggesting that these free viral DNAs are the direct precursors to the leukemia-specific proviruses. The mosaic of ecotropic and nonecotropic sequences within these unintegrated viral DNAs varies from one preleukemic thymus to another but often appears structurally homogeneous within individual thym...
Distinct chromosomal abnormalities in murine leukemia virus-induced T- and B-cell lymphomas
International Journal of Cancer, 1989
We performed a cytogenetic study on 16 murine mature B-cell lymphomas and 10 T-cell lymphomas, using G-banding techniques. All tumors, with the exception of 3 spontaneous 6-cell tumors, were induced by various slowly transforming murine leukemia viruses (MuLV). Metaphases were obtained from primary (10 6-cell tumors) and first or second transplant generation lymphomas (6 6-cell and 10 T-cell tumors), all of which were well characterized with respect to phenotypic, histologic and genotypic features. In the T-cell tumors we found relatively simple karyotypic abnormalities, including various numerical aberrations, such as trisomy 15, in line with many earlier reports. However, the majority of 6-cell tumors showed a great variety of both structural and numerical chromosomal anomalies. Three 6-cell lymphomas had an apparently normal karyotype. No single cytogenetic abnormality occurred commonly in the 6-cell lymphomas, but some structural abnormalities were found in more than one stemline, in particular, ins (I I) (Al; A2) in 3 tumors, and deletions involving the D-region of chromosome 14 in 3 other lymphomas. These cytogenetic results clearly indicate that the pathogenic mechanisms involved in MuLV-induced (long latency) 6-cell lymphomagenesis and (short latency) T-cell lymphomagenesis differ considerably. MATERIAL AND METHODS Mice, viruses and lymphomas Primary lymphomas were induced by injection of newborn C57BL or BALB/c mice with various MuLV strains (Zijlstra et al., 1984; Vasmel et al., 1988). Spontaneously developing lymphomas and lymphomas induced by a milk-transmitted Btropic ecotropic MuLV were obtained as reported (Melief et ~ 3 T~ whom reprint requests should be addressed.
Journal of virology, 1991
The Cas-Br-E murine leukemia virus is a nondefective retrovirus that induces non-T-, non-B-cell lymphomas in susceptible NIH/Swiss mice. By using a DNA probe derived from Cas-Br-E provirus-flanking sequences, we identified a DNA region, originally called Sic-1, rearranged in 16 of 24 tumors analyzed (67%). All proviruses were integrated in a DNA segment smaller than 100 bp and were in the same 5'-to-3' orientation. Ecotropic as well as mink cell focus-forming virus types were found integrated in that specific DNA region. On the basis of Southern blot analysis of somatic cell hybrids and progeny of an interspecies backcross, the Sic-1 region was localized on mouse chromosome 9 near the previously described proto-oncogenes or common viral integration sites: Ets-1, Cbl-2, Tpl-1, and Fli-1. Restriction map analysis shows that this region is identical to the Fli-1 locus identified in Friend murine leukemia virus-induced erythroleukemia cell lines and thus may contain sequences al...
Journal of Virology, 1986
We have derived hybridization probes from analogous 100-base-pair segments located within the N-terminal region of gp70 coding sequences which differentiate xenotropic from mink cell focus-forming (MCF)-related murine leukemia virus (MuLV) DNAs. The MCF probe annealed to the integrated proviruses of all six MCF MuLV isolates tested; the xenotropic probe hybridized to the DNAs of all four xenotropic proviral isolates examined. No cross-hybridization was observed, and neither probe reacted with the env segments of amphotropic or ecotropic MuLV DNAs. Southern blot analysis of HindIII- or EcoRI-digested genomic DNAs from a variety of inbred laboratory mice demonstrated the presence of more MCF- than xenotropic MuLV-related segments in every strain tested.
Molecular and cellular biology, 1987
The Gross passage A murine leukemia virus (MuLV) induced T-cell leukemia of clonal (or oligoclonal) origin in inoculated mice. To study the role of the integrated proviruses in these tumor cells, we cloned several newly integrated proviruses (with their flanking cellular sequences) from a single tumor in procaryotic vectors. With each of the five clones obtained, a probe was prepared from the cellular sequences flanking the provirus. With one such probe (SS8), we screened several Gross passage A MuLV-induced SIM.S mouse tumor DNAs and found that, in 11 of 40 tumors, a provirus was integrated into a common region designated Gin-1. A 26-kilobase-pair sequence of Gin-1 was cloned from two lambda libraries, and a restriction map was derived. All proviruses were integrated as a cluster in the same orientation within a 5-kilobase-pair region of Gin-1, and most of them had a recombinant structure of the mink cell focus-forming virus type. The frequency of Gin-1 occupancy by provirus was mu...
Virus Research, 1994
MCF1233 is an oncogenic C57BL-derived retrovirus of the Murine Leukemia Virus (MuLV) family, that causes T and B l~phomas in an MHC-associated fashion. In this study, we cloned MCF1233, determined its nucleotide sequence and, by comparison with its MuLV relatives, identified the sequences that relate to the leukemogenic character of this virus. MCF1233 was found to have an ecotropic backbone, and carried acquired polytropic sequences in the 3' pal and 5' enu region. The gag-region contained six specific nucleotides, determining the viral B-tropism. Short sequences within the U3 LTR shared specific homology with the xenotropic Bxv-1 MuLV, which is the U3 donor for ieukemogenic MCF MuLV of AKR origin. These sequences, in combination with specific ecotropic sequences present in elzu p15E, most likely determine the viral oncogenicity. Currently, the deduced MCF1233 amino sequence is being exploited for T cell epitope analysis, which in this paper is discussed with respect to antigenically distinct Friend/Moloney/Rauscher types of MuLV. Identification of these T cell epitopes will contribute to our understanding of the fundamental aspects of immune control on MCFl233-indu~d l~phomagenesis. It will help to elucidate the mechanisms that underlie immune escape of T lymphomas, rarely arising in "The nucleotide sequence data reported in this paper have been deposited with GenBank under accession No. U 13766.
Somatically acquired recombinant murine leukemia proviruses in thymic leukemias of AKR/J mice
Journal of Virology, 1983
We have probed the structure and arrangement of murine leukemia virus genomes in eight spontaneous AKR thymic leukemias by Southern hybridization with one ecotropic pol and four ecotropic env probes. These probes revealed many (in 2 cases over 15) somatically acquired proviruses that had undergone complex patterns of recombination. The large majority were not deleted and were structurally analogous to the oncogenic mink cell focus-inducing murine leukemia viruses isolated from AKR tumors in that the amino-terminal p15E-coding region derived from ecotropic AKR murine leukemia virus sequences, whereas certain gp70-coding sequences were nonecotropic. Nevertheless, we observed a few proviruses which did not appear to be gp70 recombinants; however, these proviruses were in general clearly recombinant within the p15E-coding sequences. Although the proviral recombination patterns were quite variable, in general the large majority of recombinant proviruses within each tumor appeared structu...
Journal of Virology, 1981
A specific cDNA probe of AKR murine leukemia virus (AKR-MLV) was prepared to detect AKR-MLV sequences in normal and tumor tissues in a variety of AKR mouse substrains. AKR strains contained up to six endogenous AKR-MLV genomes. All substrains tested had one AKR-MLV locus in common, and closely related substrains had several proviruses integrated in an identical site. Virus-induced tumors in the AKR/FuRdA and AKR/JS strains showed a reintegration pattern of AKR-MLV sequences unique for the individual animal, suggesting a monoclonal origin for the outgrown tumors. An analysis of tumor DNAs from the AKR/FuRdA and AKR/JS substrains with restriction enzymes cleaving within the proviral genome revealed a new EcoRI restriction site and BamHI restriction site not present in normal tissues. The positions of these sites corresponded both with cleavage sites of EcoRI and BamHI in integrated Moloney recombinants and with the structure of isolated AKR mink cell focus-forming viruses. All tumors ...
Journal of virology, 1986
Clonal selections occurring during the progression of Moloney murine leukemia virus (MuLV)-induced T-cell lymphomas in mice were examined in primary and transplanted tumors by monitoring various molecular markers: proviral integration patterns, MuLV insertions near c-myc and pim-1, and rearrangements of the immunoglobulin heavy chain and beta-chain T-cell receptor genes. The results were as follows. Moloney MuLV frequently induced oligoclonal tumors with proviral insertions near c-myc or pim-1 in the independent clones. Moloney MuLV acted as a highly efficient insertional mutagen, able to activate different (putative) oncogenes in one cell lineage. Clonal selections during tumor progression were frequently marked by the acquisition of new proviral integrations. Independent tumor cell clones exhibited a homing preference upon transplantation in syngeneic hosts and were differently affected by the route of transplantation.