title: Coexpression of normally incompatible developmental pathways in retinoblastoma genesis.
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.
authors.affiliation: Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Justina
authors.initials: J
authors.lastname: McEvoy
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Flores-Otero
authors.forename: Jiakun
authors.initials: J
authors.lastname: Zhang
authors.forename: Katie
authors.initials: K
authors.lastname: Nemeth
authors.forename: Rachel
authors.initials: R
authors.lastname: Brennan
authors.forename: Cori
authors.initials: C
authors.lastname: Bradley
authors.forename: Fred
authors.initials: F
authors.lastname: Krafcik
authors.forename: Carlos
authors.initials: C
authors.lastname: Rodriguez-Galindo
authors.forename: Matthew
authors.initials: M
authors.lastname: Wilson
authors.forename: Shunbin
authors.initials: S
authors.lastname: Xiong
authors.forename: Guillermina
authors.initials: G
authors.lastname: Lozano
authors.forename: Julien
authors.initials: J
authors.lastname: Sage
authors.forename: Ligia
authors.initials: L
authors.lastname: Fu
authors.forename: Lotfi
authors.initials: L
authors.lastname: Louhibi
authors.forename: Jeff
authors.initials: J
authors.lastname: Trimarchi
authors.forename: Amar
authors.initials: A
authors.lastname: Pani
authors.forename: Richard
authors.initials: R
authors.lastname: Smeyne
authors.forename: Dianna
authors.initials: D
authors.lastname: Johnson
authors.forename: Michael A
authors.initials: MA
authors.lastname: Dyer
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D020869:Gene Expression Profiling; D005838:Genotype; D006801:Humans; D051379:Mice; D012175:Retinoblastoma / Q000235:genetics / Q000473:pathology*