M-MuLV-induced leukemogenesis: Integration and structure of recombinant proviruses in tumors |
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Authors: | Herman van der Putten Wim Quint Janny van Raaij Els Robanus Maandag Inder M Verma Anton Berns |
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Institution: | 1. Department of Biochemistry University of Nijmegen Geert Grooteplein N21 6525 EZ Nijmegen, The Netherlands;2. Salk Institute for Biological Studies P.O. Box 85800 San Diego, California 92138 USA |
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Abstract: | M-MuLV-specific DNA probes were used to establish the state of integration and amplification of recombinant proviral sequences in Moloney virus-induced tumors of Balb/Mo, Balb/c and 129 mice. The somatically acquired viral sequences contain both authentic M-MuLV genomes and recombinants of M-MuLV with endogenous viral sequences. All reintegrated genomes carry long terminal repeat (LTR) sequences at both termini of their genome. In the preleukemic stage a large population of cells exhibiting a random distribution of reintegrated M-MuLV genomes are seen, but during outgrowth of the tumor, selection of cells occurs leaving one or a few clonal descendants in the outgrown tumor. In this latter stage recombinant genomes can be detected. Although these recombinants constitute a heterogeneous group of proviruses, characteristic molecular markers are conserved among many individual proviral recombinants, lending credence to the notion that a certain recombinant structure is a prerequisite for the onset of neoplasia. The structure of these recombinants shows close structural similarities to the previously described mink cell focus-inducing (MCF)-type viruses. |
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