The clonal origin and clonal evolution of epithelial tumours

While the origin of tumours, whether from one cell or many, has been a sour ce of fascination for experimental oncologists for some time, in recent yea rs there has been a veritable explosion of information about the clonal arc hitecture of tumours and their antecedents, stimulated, in the main, by the ready accessibility of new molecular techniques. While most of these new r esults have apparently confirmed the monoclonal origin of human epithelial (and other) tumours, there are a significant number of studies in which thi s conclusion just cannot be made. Moreover, analysis of many articles show that the potential impact of such considerations as patch size and clonal e volution on determinations of clonality have largely been ignored, with the result that a number of these studies are confounded. However, the clonal architecture of preneoplastic lesions provide some interesting insights - m any lesions which might have been hitherto regarded as hyperplasias are app arently clonal in derivation. If this is indeed true, it calls into some qu estion our hopeful corollary that a monoclonal origin presages a neoplastic habitus. Finally, it is clear, for many reasons, that methods of analysis which involve the disaggregation of tissues, albeit microdissected, are far from ideal and we should be putting more effort into techniques where the clonal architecture of normal tissues, preneoplastic and preinvasive lesion s and their derivative tumours can be directly visualized in situ.