Cancer: The origin of human retinoblastoma.

Abstract

The cellular origins of most human cancers remain unknown, but an analysis of embryonic retinal cells identifies differentiating cones as the cell of origin for the childhood cancer retinoblastoma. See Letter p.385 Inactivation of both alleles of the retinoblastoma (RB) gene generally leads to the formation of retinoblastomas, but rarely to other tumour types. David Cobrinik and colleagues now provide an explanation for this in a study that identifies the human retinal cell-of-origin from which retinoblastomas arise. They find that of the various human retinal cell types, cone precursor cells are uniquely sensitive to transformation upon loss of RB. This is due to the cone precursor cell-specific molecular framework, for example, the high expression levels of MDM2 and MYCN which can collaborate with RB loss. These principles may more generally explain why certain initiating oncogenic mutations tend to be associated with specific cancer types.