Impact of Foreign DNA Integration on Tumor Biology and on Evolution via Epigenetic Alterations

Abstract

The insertion of foreign DNA into mammalian genomes can alter their methylation and transcription patterns at remote sites from the locus of foreign DNA integration. The mechanisms leading to these fundamental changes and their frequencies are unknown. Sites and extent of changes in the recipient cells might depend on the location of foreign DNA integration. In the second part of this review, it will be hypothesized that the insertion event itself, for example, of tumor viral DNA via its epigenetic genome-wide consequences, plays an important role in oncogenesis. During evolution, the impact of ancient retrotransposon or retroviral genomes and the ensuing epigenetic alterations in the recipient genomes might have generated cells with completely different transcriptional profiles. Due to the continued presence of the transgenomes these alterations were genetically stable and were selected for or against by the environmental conditions prevalent at the time. These evolutionary effects are very different from those postulated for insertional mutagenesis, added genetic information or regulatory elements placed into the vicinity of cellular functions.

KEYWORDS::

• de novo methylation of integrated foreign DNA
• DNA integration and remote epigenetic factors
• DNA methylation
• new hypothesis on retroviruses in evolution
• remote epigenetic effects in (viral) oncology

Financial & competing interests disclosure

The author‘s current work is supported by the Deutsche Forschungsgemeinschaft (DFG), Bonn, Germany and the Thyssen Foundation, Köln, Germany. W Doerfler is Professor Emeritus (University of Cologne, Germany) and guest professor in the Institute for Clinical and Molecular Virology, Erlangen University Medical School. Previous projects carried out in the Institute of Genetics in Cologne, were made possible, at different times, by grants from the DFG (SFB 74 and 274), from the Center for Molecular Medicine Cologne (CMMC, TP13), and from the Thyssen, Sander and Humboldt Foundations. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

The author‘s current work is supported by the Deutsche Forschungsgemeinschaft (DFG), Bonn, Germany and the Thyssen Foundation, Köln, Germany. W Doerfler is Professor Emeritus (University of Cologne, Germany) and guest professor in the Institute for Clinical and Molecular Virology, Erlangen University Medical School. Previous projects carried out in the Institute of Genetics in Cologne, were made possible, at different times, by grants from the DFG (SFB 74 and 274), from the Center for Molecular Medicine Cologne (CMMC, TP13), and from the Thyssen, Sander and Humboldt Foundations. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.