Molecular Cytogenetics in the Study of Cancer

Abstract

Cancer is a genetic disease in which cells accumulate enough damage in their genome to both deregulate their growth and to allow unlimited division. Until recent years our ability to study and describe these genetic defects relied largely on the analysis of banded chromosomes. Chromosome banding is generally an efficient low-cost screening technique, and its use has identified the importance of losses and gains of chromosomes and of specific translocations in the natural history of cancer. However, it has a number of limitations, which have made the development of complementary techniques necessary. First, it requires that the malignant cells can be brought to divide outside the human body, i.e., in culture. This requirement is often not possible with neoplasms other than the leukaemias and lymphomas, and consequently the body of chromosome banding data on cancer cells is mainly based on studies of cells from these diseases, although they constitute only a small fraction of all human cancers. Second, the resolution of banding analysis is for obvious reasons roughly one chromosome band, and since a typical band contains millions of bases and hundreds of genes, that is a rather low resolution. Third, the technique only identifies two qualities — dark and light bands — and so two dark bands or two light bands may be mistaken for each other. Revision of chromosome banding data using molecular cytogenetics has shown that such mistakes are in fact rather common.