Putting oncogenes into a developmental context.

Abstract

Cancer is largely caused by genomic events that activate oncogenes or inactivate tumor suppressor genes. To date, the mechanisms by which these mutant gene products contribute to tumorigenesis has been studied mostly in experimental model systems that have not been able to interrogate the potential contribution of developmental factors in the etiology of neoplasia. Recently, we employed a conditional transgenic model system to demonstrate that the ability of the MYC oncogene to induce tumorigenesis is influenced by the developmental age of the host. MYC induced in embryonic of neonatal tissues cellular proliferation and the rapid onset of tumorigenesis; whereas MYC activation in adult tissues induces cellular hypertrophy. Thus, differences in the frequency and spectrum of cancers observed in different aged hosts may reflect the influence of developmental context. Cancer may generally be better thought of as a consequence of genetic events that occur in a permissive epigenetic state. Developmental context may be a critical determinant in the pathogenesis of neoplasia.