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Title: Coexpression of Normally Incompatible Developmental Pathways in Retinoblastoma Genesis [mouse model data]      
keywords:
Transcriptome or Gene expression
ID:
PRJNA153847
description:
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. Overall design: 132 mouse model primary retinoblastoma tumor Samples
accesstypes:
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landingpage: http://www.ncbi.nlm.nih.gov/bioproject/PRJNA153847
authentication:
none
authorization:
none
ID:
pmid:21840489
dateReleased:
06-07-2011
name:
Mus musculus
ncbiID:
ncbitax:10090
abbreviation:
NCBI
homePage: http://www.ncbi.nlm.nih.gov
ID:
SCR:006472
name:
National Center for Biotechnology Information
homePage: http://www.ncbi.nlm.nih.gov/bioproject
ID:
SCR:004801
name:
NCBI BioProject
  • R01 EY018599/EY/NEI NIH HHS/United States

  • CA21765/CA/NCI NIH HHS/United States

  • R01 EY014867/EY/NEI NIH HHS/United States

  • R01 CA168875/CA/NCI NIH HHS/United States

  • CA114102/CA/NCI NIH HHS/United States

  • Howard Hughes Medical Institute/United States

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