A common integration locus in type B retrovirus-induced thymic lymphomas

Abstract

Type-B leukemogenic retrovirus (TBLV) is a replication-competent type-B thymotropic retrovirus which lacks a transforming gene and whose genome is > 98% homologous to that of type-B mouse mammary tumor virus (MMTV). In contrast to MMTV, which induces mammary adenocarcinomas, TBLV induces a high incidence of T-cell thymic lymphomas in mice after a very short latent period. To investigate the molecular mechanisms by which TBLV induces T-cell lymphomas, we screened TBLV-induced tumor DNA for the frequent disruption of a particular cellular locus by TBLV proviral copies. In approximately 20% of the 55 primary tumors screened, the presence of proviruses in a common integration site was detected. This locus spans at least 53 kb of genomic DNA and maps to the mouse X chromosome. The presence of a functional gene at this locus is suggested by the conservation of nucleotide sequences from this locus among diverse animal species and by the expression of these sequences as mRNA in normal mouse tissues and tumors. The majority (17/18) of TBLV-induced primary tumors examined have elevated levels of this expressed mRNA.