Fig. 1: Late-onset and early-onset retinoblastoma cells are highly similar to proliferating retinoblastoma progenitor cells.

Immunohistochemical and principal component (PC) analysis indicate that early retinoblastoma tumors are highly similar to normal retinal progenitor cells. A Post-natal day 0 (P0) and P7 retinae were collected from control (Vsx2+), Vsx2+; Rbfl/fl; p107−/− (late-onset retinoblastoma model), and from Vsx2+; Rbfl/fl; p107−/−; Ptenfl/fl (early-onset bilateral tumors). Sections were stained with hematoxylin and eosin (H&E), or by immunohistochemistry with antibodies that stain Ki67 to detect proliferation or active, cleaved caspase-3 (Casp3) to detect apoptosis. B Principle component analysis of all samples, displaying PC #1 and PC #2. Three retinae from P7 Vsx2+; Rbfl/fl (SKO) mice were also harvested for simultaneous analysis. Post-mitotic, differentiated control (P7) retinae separated from all proliferating samples on PC #1, with ΔRb showing an intermediate phenotype on this axis. ΔRb/p107/Pten-deficient P7 retinae were the only samples separated from all other samples, particularly control, on PC #2. The individual genotypes are represented by color and the timepoints are represented by shape for the control Vsx2+ (CHX), Vsx2+; Rbfl/fl (SKO), Vsx2+; Rbfl/fl; p107−/− (DKO), and from Vsx2+; Rbfl/fl; p107−/−; Ptenfl/fl (TKO) sorted retinal tissues.