Small tumor virus genomes are integrated near nuclear matrix attachment regions in transformed cells

More than 15% of human cancers have a viral etiology. In benign lesions ind uced by the small DNA tumor viruses, viral genomes are typically maintained extrachromosomally. Malignant progression is often associated with viral i ntegration into host cell chromatin. To study the role of viral integration in tumorigenesis, we analyzed the positions of integrated viral genomes in tumors and tumor cell lines induced by the small oncogenic viruses, includ ing the high-risk human papillomaviruses, hepatitis B virus, simian virus 4 0, and human T-cell leukemia virus type 1. We show that viral integrations in tumor cells lie near cellular sequences identified as nuclear matrix att achment regions (MARs), while integrations in nonneoplastic cells show no s ignificant correlation with these regions. In mammalian cells, the nuclear matrix functions in gene expression and DNA replication. MARs play varied b ut poorly understood roles in eukaryotic gene expression. Our results sugge st that integrated tumor virus genomes are subject to MAR-mediated transcri ptional regulation, providing insight into mechanisms of viral carcinogenes is. Furthermore, the viral oncoproteins serve as invaluable tools for the s tudy of mechanisms controlling cellular growth. Similarly, our demonstratio n that integrated viral genomes may be subject to MAR-mediated transcriptio nal effects should facilitate elucidation of fundamental mechanisms regulat ing eukaryotic gene expression.