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Coexpression of Normally Incompatible Developmental Pathways in Retinoblastoma Genesis

2011; Cell Press; Volume: 20; Issue: 2 Linguagem: Inglês

10.1016/j.ccr.2011.07.005

1878-3686

Justina McEvoy, Jacqueline Flores‐Otero, Jiakun Zhang, Katie Nemeth, Rachel C. Brennan, Cori Bradley, Fred Krafcik, Carlos Rodríguez‐Galindo, Matthew W. Wilson, Shunbin Xiong, Guillermina Lozano, Julien Sage, Ligia Fú, Lotfi Louhibi, Jeffrey M. Trimarchi, Amar K. Pani, Richard J. Smeyne, Dianna A. Johnson, Michael A. Dyer,

Cancer-related Molecular Pathways

It is widely believed that the molecular and cellular features of a tumor reflect its cell of origin and can thus provide clues about treatment targets. The retinoblastoma cell of origin has been debated for over a century. Here, we report that human and mouse retinoblastomas have molecular, cellular, and neurochemical features of multiple cell classes, principally amacrine/horizontal interneurons, retinal progenitor cells, and photoreceptors. Importantly, single-cell gene expression array analysis showed that these multiple cell type-specific developmental programs are coexpressed in individual retinoblastoma cells, which creates a progenitor/neuronal hybrid cell. Furthermore, neurotransmitter receptors, transporters, and biosynthetic enzymes are expressed in human retinoblastoma, and targeted disruption of these pathways reduces retinoblastoma growth in vivo and in vitro.