Experimental Pathology and Breast Cancer Genetics: New Technologies

Abstract

A silent revolution is taking place that has the potential to have an enormous impact on medicine, but it requires a high investment in technology and research before it can be of practical use. The reason for the silence is the high cost of the technology involved, putting it out of the reach of most academic centres. With the realisation that all of the human genes will be known and sequenced in the next few years, the next objective is to harness this information to identify new drug targets, to improve methods of diagnosis and to identify inherited genetic differences that increase the risk of developing particular diseases (Karp and Broder 1995). This will also facilitate analysis of the interaction of environmental factors and genetics. The way is being led by biotechnology and pharmaceutical companies and the larger institutes such as the National Cancer Institute (NCI). At the NCI, part of Klausner’s strategic planning was to establish the ‘genome anatomy project’ (see website http://inhouse.ncbi.nlm.nih.gov/ncicgap/). Such strategic planning was anathema to many scientists, but it must be the way forward in some areas of science where number crunching is the order of the day. Even though most doctors are not aware of the future applications, investors are clamouring to have a slice of the action, as indicated by a recent issue of Business Week that was devoted entirely to ‘The Biotech Century’. For academics wishing to be involved there is the difficulty that alone they cannot afford the capital costs, while by collaborating with industry it is difficult to get a deal that enables the information gained to go directly into the public domain. The NCI initiative is very important, as everything is being released over their website, including detailed protocols, and most of the current technology is being directed at diagnosing mutations in known genes or looking at mRNAs that are expressed in different disease states to obtain a profile or ‘index’ of the tissue or tumour involved (Brown and Hartwell 1998). The limitations are related to sensitivity and representation of the RNAs isolated from small numbers of cells where an amplification procedure is required. In addition, RNA levels do not directly relate to protein expression, and studies of RNA will not identify mutations or subtle changes in proteins that may be of more importance, such as phosphorylation and glycosylation. Many companies in the last 2 years have therefore started to direct their attention to expression profiling at the protein level, and if the difficulties of sensitivity can be overcome, this may prove to be the best way forward for some applications (Strachan et al. 1997).