Novel Endogenous Retroviral Genomes in Human Genomic DNA

Abstract

Human breast neoplasia remains the major cause of cancer related deaths in women. Unfortunately little information is available about the causes and nature of this disease. Several laboratories have searched for a common element associated with human breast cancer (1). Early studies suggested that a retrovirus resembling the mouse mammary tumor virus (MMTV) might be expressed in human mammary tumors. However, attempts to identify RNA related to MMTV in human breast tumor tissue met with variable success (2, 3) due to the poor quality of available DNA probes and the insensitivity of the techniques used to quantitate or detect DNA/RNA hybrids. In recent years using recombinant MMTV DNA (4, 5) and low stringency blot hybridization conditions (6, 7), sequences homologous to MMTV have been detected in human DNA (7, 8). Here we describe the isolation and characterization of a human recombinant clone (HLM-2) which contains sequences related to the MMTV genome. Analysis of HLM-2 and other related clones has shown the following: (a) the human MMTV related sequences are organized in a manner expected for a genetically transmitted provirus; (b) the human proviral genome contains a mosaic of sequences characteristic of different retroviral genera; (c) the HLM-2 proviral genome is representative of a large family of endogenous retroviral genomes; and (d) this class of endogenous retroviruses has been intimately associated with primates throughout much of their evolution.