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Cell Stem Cell DOI:10.1016/j.stem.2010.03.016

Wilms tumor chromatin profiles highlight stem cell properties and a renal developmental network.

Publication TypeJournal Article
Year of Publication2010
AuthorsAiden, APresser, Rivera, MN, Rheinbay, E, Ku, M, Coffman, EJ, Truong, TT, Vargas, SO, Lander, ES, Haber, DA, Bernstein, BE
JournalCell Stem Cell
Date Published2010 Jun 04
KeywordsAdaptor Proteins, Signal Transducing, Cell Differentiation, Cell Transformation, Neoplastic, Chromatin, Chromatin Immunoprecipitation, DNA Methylation, Embryonic Stem Cells, Gene Expression Regulation, Developmental, Gene Regulatory Networks, Genome-Wide Association Study, Humans, Kidney, Kidney Neoplasms, Mutation, Neoplasm Proteins, Organ Specificity, Transcription, Genetic, Tumor Suppressor Proteins, Wilms Tumor

Wilms tumor is the most common pediatric kidney cancer. To identify transcriptional and epigenetic mechanisms that drive this disease, we compared genome-wide chromatin profiles of Wilms tumors, embryonic stem cells (ESCs), and normal kidney. Wilms tumors prominently exhibit large active chromatin domains previously observed in ESCs. In the cancer, these domains frequently correspond to genes that are critical for kidney development and expressed in the renal stem cell compartment. Wilms cells also express "embryonic" chromatin regulators and maintain stem cell-like p16 silencing. Finally, Wilms and ESCs both exhibit "bivalent" chromatin modifications at silent promoters that may be poised for activation. In Wilms tumor, bivalent promoters correlate to genes expressed in specific kidney compartments and point to a kidney-specific differentiation program arrested at an early-progenitor stage. We suggest that Wilms cells share a transcriptional and epigenetic landscape with a normal renal stem cell, which is inherently susceptible to transformation and may represent a cell of origin for this disease.


Alternate JournalCell Stem Cell
PubMed ID20569696
PubMed Central IDPMC2897075
Grant ListP50CA101942 / CA / NCI NIH HHS / United States
U54 HG004570-02 / HG / NHGRI NIH HHS / United States
P50 CA101942 / CA / NCI NIH HHS / United States
U54 HG004570-01 / HG / NHGRI NIH HHS / United States
R37 CA058596 / CA / NCI NIH HHS / United States
U54 HG004570 / HG / NHGRI NIH HHS / United States
R37CA058596 / CA / NCI NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
K08 DK080175 / DK / NIDDK NIH HHS / United States
K08DK080175 / DK / NIDDK NIH HHS / United States