Amplification of DNA Sequences in Mammalian Cells

This chapter discusses the aberrant DNA sequence amplification processes that occur in mammalian cells because of the clinical relevance to drug resistance and oncogene amplification in tumors and because the underlying mechanisms seem close to being understood at the molecular level. What seemed to be a relatively esoteric mutational phenomenon is now a major determining factor in the genesis of cancer, as well as a serious deterrent to successful chemotherapeutic drug treatment regimens. The chapter traces the history of the discovery of DNA sequence amplification, cites several examples, and discusses the similarities and differences among these systems. Important methodologies developed for studying amplified sequences are also presented in the chapter. It reviews the viable models that attempt to explain the phenomenon in mammalian cells and shows the way the resolution of the underlying molecular mechanisms of amplification promises to teach much about both normal and aberrant chromosome dynamics (e. g., replication, recombination and repair processes, and chromosomal breakage and healing).