DNA amplification in drug resistant cells and in tumours

Abstract

DNA amplification is a pervasive phenomenon in continuous cell lines and in tumours. It can occur in many different parts of the genome with high frequency, and a very large amount of DNA, probably including many genes, is often involved in a single amplification event. In tumours, it is likely that a common mechanism underlies the amplification of genes which confer drug resistance and genes which give a growth advantage to the tumour. DNA amplification may be caused by defects in the regulation of DNA replication, and similar defects may lead to other chromosomal abnormalities such as translocations, inversions and heteroploidy. Two recent observations should facilitate identification and study of the underlying defects: agents or treatments which damage DNA can increase the rate of amplification, and mutant cell lines can be selected which amplify their DNA at a greatly increased frequency.