An immature, dedifferentiated, and lineage-deconstrained cone precursor origin of N-Myc-initiated retinoblastoma.

ABSTRACT: Most retinoblastomas develop from maturing cone precursors in response to biallelic RB1 loss and are dependent on cone maturation-related signaling. Additionally, ∼2% lack RB1 mutations but have MYCN amplification (MYCN^A), N-Myc protein overexpression, and more rapid and invasive growth, yet the MYCN^A retinoblastoma cell of origin and basis for its responses to deregulated N-Myc are unknown. Here, using explanted cultured retinae, we show that ectopic N-Myc induces cell cycle entry in cells expressing markers of several retinal types yet induces continuous proliferation and tumorigenesis only in cone precursors. Unlike the response to RB1 loss, both immature cone arrestin-negative (ARR3^-) and maturing ARR3⁺

SUBMITTER: Singh HP 

PROVIDER: S-EPMC9282279 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature