Expression signatures obtained from tumour samples are widely used to characterise tumour subtypes and to provide prognostic information. This commentary, based on a recent paper, questions the scientific validity of such signatures as a means of understanding the underlying biology.

Almost every human disease has both a genetic and an environmental component. Even a classical inherited condition such as hemophilia can be influenced by external factors—in fact, most of the pathogenic effects of the mutation can be avoided by judicious injections of clotting factor, leading to a nearly normal life expectancy. For infectious diseases, often considered as essentially environmental, there are well-documented inherited differences in susceptibility, one of the most striking being the resistance to HIV infection of homozygous carriers of (...) the delta-32 mutation in the CCR5 gene (Dragic et al. 1996). Nevertheless, a number of conditions are “mostly genetic,” others “mostly environmental,” while many .. (shrink)