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Cancer Cell. 2011 Aug 16;20(2):260-75. doi: 10.1016/j.ccr.2011.07.005.

Coexpression of normally incompatible developmental pathways in retinoblastoma genesis.

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  • 1Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.

Abstract

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.

Copyright © 2011 Elsevier Inc. All rights reserved.

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PMID:
21840489
[PubMed - indexed for MEDLINE]
PMCID:
PMC3551581
Free PMC Article

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