Stochastic gene expression, disruption of tissue averaging effects and cancer as a disease of development.

Despite the extensive literature describing the somatic genetic alterations in cancer cells, the precise origins of cancer cells remain controversial. In this article, I suggest that the etiology of cancer and the generation of genetic instability in cancer cells should be considered in the light of recent findings on both the stochastic nature of gene expression and its regulation at tissue level. By postulating that gene expression is intrinsically probabilistic and that stabilization of gene expression arises by cellular interactions in "morphogenetic fields", development and cellular differentiation can be rethought in an evolutionary perspective. In particular, this article proposes that disruptions of cellular interactions are the initial source of abnormal gene expression in cancer cells. Consequently, cancer phenotypes such as genetic and epigenetic instabilities, and also the presence of cells with stem cell-like properties, may result from inaccurate and aberrant patterns of gene expression generated by microenvironmental alterations. Finally, the therapeutic implications of this view are discussed. (c) 2005 Wiley Periodicals, Inc.