Nucleic acid based techniques for the detection of rare cancer cells in clinical samples

Solid tumors evolve from cells which have lost control functions safeguardi ng their genomic integrity by mutation within specific genes. Consequently, proliferating cells within a tumor differ slightly from generation to gene ration. This permits the continuous production of new and subsequent select ion of the best adapted cells, which retain this capacity of self-evolution . The threat of neoplastic diseases is due to the clinical experience, that surgical resection of all cells with this potential for autonomous evoluti on is often not achievable, since they were spread to distant non-resectabl e sites in the organism before diagnosis and surgical removal of the primar y tumor and might later grow out as metastatic lesion. Lack of diagnostic t echniques to detect small preneoplastic lesions as well as single spread ca ncer cells often causes delayed diagnosis when curative therapy is no longe r achievable. Recent advances in characterizing the molecular basis of geno mic instability, identifying specific gatekeeper mutations and their functi onal consequences in neoplastic cells now permit the development of new hig hly sensitive tests to identify preneoplastic lesions as well as spread sin gle cancer cells. These techniques carry a tremendous potential for simple cost effective cancer early detection and screening assays as well as for d iagnostic applications to identify spread cancer cells. Thus, they most lik ely will soon guide indication for surgical and adjuvant therapy protocols for patients with preneoplastic or neoplastic lesions. However, due to the complexity of the assays and the great variety of technical aspects involve d almost all diagnostic applications are not yet standardized. This poses s ignificant problems for quality control as well as inter-laboratory compara bility of the results and underlines the urgent demand for well controlled collaborative efforts to evaluate indications and diagnostic standards for these assays. Here, the theoretical background, basic principles and some d iagnostic applications of these new tests are reviewed.