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.

Figure 1. The cone stands alone

Human retinal progenitor cells give rise to seven distinct cell types. Retinoblastoma develops specifically from differentiating cone precursors, owing to the molecular circuitry in these cells, which includes high expression of N-Myc, SKP2 and MDM2 proteins. This expression pattern permits the cells to proliferate and undergo a cancerous transformation when the tumour-suppressor protein RB is lost. In other retinal cell types, loss of RB either has no detectable effect or induces cell death (not shown).