ABSTRACT
With the publication of the results of the Human Genome Project, near-complete sequence information has become available theoretically to permit presymptomatic screening of all genes identified as relevant to cancer risk for the presence of heritable variation. This would include not only high-penetrance mutations but also polymorphic variants influencing cancer risk to a lesser degree. However, before genetic screening on such a large scale becomes a serious option, several issues remain to be addressed. The predominant issue in this respect is the clinical utility of genetic screening as standard practice. That is, does it reduce cancer morbidity and mortality through interventions that decrease cancer risk? Although genetic screening does exactly that in some isolated cases, at this stage it is fair to say that for many cancers the clinical validity and utility of such testing is debatable and more data are needed.1 While these issues are dealt with elsewhere in this book, the central question in this chapter is whether the state of current mutation analysis technology is actually capable of meeting the potential demand for large-scale genetic screening (for earlier reviews of the subject, see Mathew,2 and Eng and Vijg3). Here, we will address the issue by first discussing the various criteria for an optimal genetic screening test in relation to its application. We will then present an overview of current and experimental methods for the
detection of point mutations and small insertions, and deletions in clinical diagnostics. Finally, the future technological prospects in this field will be discussed.
