Dataset Information


Coexpression of Normally Incompatible Developmental Pathways in Retinoblastoma Genesis [human tumor/cell line data]

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. Importantly, 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. Our finding that retinoblastoma tumor cells express multiple neuronal differentiation programs that are normally incompatible in development suggests that the pathways that control retinal development and establish distinct cell types are perturbed during tumorigenesis. Therefore, the cell-of-origin for retinoblastoma cannot be inferred from the features of the tumor cells themselves. However, we now have a detailed understanding of the neuronal pathways that are deregulated in retinoblastoma and targeting the catecholamine and indolamine receptors or downstream components could provide useful therapeutic approaches in future studies. This example highlights the importance of comprehensive molecular, cellular and physiological characterization of human cancers with single cell resolution as we incorporate molecular targeted therapy into treatment regimens. 55 primary pediatric retinoblastoma tumors were collected and assayed and compared to with 3 passaged xenografts and 4 RB cell lines

ORGANISM(S): Homo sapiens  

SUBMITTER: Julien Sage   Lotfi Louhibi  Jiakun Zhang  Amar Pani  Matthew Wilson  Justina McEvoy  Shunbin Xiong  Fred Krafcik  Rachel Brennan  Cori Bradley  David Finkelstein  Michael A Dyer  Dianna Johnson  Richard Smeyne  Katie Nemeth  Ligia Fu  Jeff Trimarchi  Guillermina Lozano  Jacqueline Flores-Otero  Carlos Rodriguez-Galindo 

PROVIDER: E-GEOD-29683 | ArrayExpress | 2011-06-07