Wilms Tumor Chromatin Profiles Highlight Stem Cell Properties and a Renal Developmental Network

Overview

Journal Cell Stem Cell

Publisher Cell Press

Specialty Cell Biology

Date 2010 Jun 24

PMID 20569696

Citations 46

Authors

Aviva Presser Aiden

Miguel N Rivera

Esther Rheinbay

Manching Ku

Erik J Coffman

Thanh T Truong

Sara O Vargas

Eric S Lander

Daniel A Haber

Bradley E Bernstein

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Modeling high-risk Wilms tumors enables the discovery of therapeutic vulnerability.

Ma G, Gao A, Chen J, Liu P, Sarda R, Gulliver J Cell Rep Med. 2024; 5(10):101770.

PMID: 39368485 PMC: 11513831. DOI: 10.1016/j.xcrm.2024.101770.

Altered binding affinity of SIX1-Q177R correlates with enhanced WNT5A and WNT pathway effector expression in Wilms tumor.

Stevenson M, Phanor S, Patel U, Gisselbrecht S, Bulyk M, OBrien L Dis Model Mech. 2023; 16(11).

PMID: 37815464 PMC: 10668032. DOI: 10.1242/dmm.050208.

Overactivation of histone deacetylases and EZH2 in Wilms tumorigenesis.

Chen C, Ngo N, Wang A, El-Dahr S, Liu H Genes Dis. 2023; 10(5):1783-1786.

PMID: 37492702 PMC: 10363625. DOI: 10.1016/j.gendis.2022.10.026.

EWSR1-ATF1 dependent 3D connectivity regulates oncogenic and differentiation programs in Clear Cell Sarcoma.

Moller E, Praz V, Rajendran S, Dong R, Cauderay A, Xing Y Nat Commun. 2022; 13(1):2267.

PMID: 35477713 PMC: 9046276. DOI: 10.1038/s41467-022-29910-4.

JARID2 and AEBP2 regulate PRC2 in the presence of H2AK119ub1 and other histone modifications.

Kasinath V, Beck C, Sauer P, Poepsel S, Kosmatka J, Faini M Science. 2021; 371(6527).

PMID: 33479123 PMC: 7993630. DOI: 10.1126/science.abc3393.

References

Ogawa O, Eccles M, Szeto J, McNoe L, Yun K, Maw M . Relaxation of insulin-like growth factor II gene imprinting implicated in Wilms' tumour. Nature. 1993; 362(6422):749-51. DOI: 10.1038/362749a0. View

Shen X, Kim W, Fujiwara Y, Simon M, Liu Y, Mysliwiec M . Jumonji modulates polycomb activity and self-renewal versus differentiation of stem cells. Cell. 2010; 139(7):1303-14. PMC: 2810107. DOI: 10.1016/j.cell.2009.12.003. View

Ohm J, McGarvey K, Yu X, Cheng L, Schuebel K, Cope L . A stem cell-like chromatin pattern may predispose tumor suppressor genes to DNA hypermethylation and heritable silencing. Nat Genet. 2007; 39(2):237-42. PMC: 2744394. DOI: 10.1038/ng1972. View

Ku M, Koche R, Rheinbay E, Mendenhall E, Endoh M, Mikkelsen T . Genomewide analysis of PRC1 and PRC2 occupancy identifies two classes of bivalent domains. PLoS Genet. 2008; 4(10):e1000242. PMC: 2567431. DOI: 10.1371/journal.pgen.1000242. View

Li W, Duan R, Kooy F, Sherman S, Zhou W, Jin P . Germline mutation of microRNA-125a is associated with breast cancer. J Med Genet. 2009; 46(5):358-60. DOI: 10.1136/jmg.2008.063123. View

Mugford J, Sipila P, McMahon J, McMahon A . Osr1 expression demarcates a multi-potent population of intermediate mesoderm that undergoes progressive restriction to an Osr1-dependent nephron progenitor compartment within the mammalian kidney. Dev Biol. 2008; 324(1):88-98. PMC: 2642884. DOI: 10.1016/j.ydbio.2008.09.010. View

Kobayashi A, Valerius M, Mugford J, Carroll T, Self M, Oliver G . Six2 defines and regulates a multipotent self-renewing nephron progenitor population throughout mammalian kidney development. Cell Stem Cell. 2008; 3(2):169-81. PMC: 2561900. DOI: 10.1016/j.stem.2008.05.020. View

Kurotaki N, Imaizumi K, Harada N, Masuno M, Kondoh T, Nagai T . Haploinsufficiency of NSD1 causes Sotos syndrome. Nat Genet. 2002; 30(4):365-6. DOI: 10.1038/ng863. View

Guttman M, Amit I, Garber M, French C, Lin M, Feldser D . Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature. 2009; 458(7235):223-7. PMC: 2754849. DOI: 10.1038/nature07672. View

10.

Bergemann A, Cole F, Hirschhorn K . The etiology of Wolf-Hirschhorn syndrome. Trends Genet. 2005; 21(3):188-95. DOI: 10.1016/j.tig.2005.01.008. View

11.

Yusenko M, Kuiper R, Boethe T, Ljungberg B, Geurts van Kessel A, Kovacs G . High-resolution DNA copy number and gene expression analyses distinguish chromophobe renal cell carcinomas and renal oncocytomas. BMC Cancer. 2009; 9:152. PMC: 2686725. DOI: 10.1186/1471-2407-9-152. View

12.

Li B, Carey M, Workman J . The role of chromatin during transcription. Cell. 2007; 128(4):707-19. DOI: 10.1016/j.cell.2007.01.015. View

13.

Kouzarides T . Chromatin modifications and their function. Cell. 2007; 128(4):693-705. DOI: 10.1016/j.cell.2007.02.005. View

14.

Wu W, Lin Z, Zhuang Z, Liang X . Expression profile of mammalian microRNAs in endometrioid adenocarcinoma. Eur J Cancer Prev. 2008; 18(1):50-5. DOI: 10.1097/CEJ.0b013e328305a07a. View

15.

Moore M, Klein R, Farinas I, Sauer H, Armanini M, Phillips H . Renal and neuronal abnormalities in mice lacking GDNF. Nature. 1996; 382(6586):76-9. DOI: 10.1038/382076a0. View

16.

Weksberg R, Shen D, Fei Y, Song Q, Squire J . Disruption of insulin-like growth factor 2 imprinting in Beckwith-Wiedemann syndrome. Nat Genet. 1993; 5(2):143-50. DOI: 10.1038/ng1093-143. View

17.

Kreidberg J, Sariola H, LORING J, Maeda M, Pelletier J, Housman D . WT-1 is required for early kidney development. Cell. 1993; 74(4):679-91. DOI: 10.1016/0092-8674(93)90515-r. View

18.

He J, Kallin E, Tsukada Y, Zhang Y . The H3K36 demethylase Jhdm1b/Kdm2b regulates cell proliferation and senescence through p15(Ink4b). Nat Struct Mol Biol. 2008; 15(11):1169-75. PMC: 2612995. DOI: 10.1038/nsmb.1499. View

19.

Nimura K, Ura K, Shiratori H, Ikawa M, Okabe M, Schwartz R . A histone H3 lysine 36 trimethyltransferase links Nkx2-5 to Wolf-Hirschhorn syndrome. Nature. 2009; 460(7252):287-91. DOI: 10.1038/nature08086. View

20.

Bardeesy N, Falkoff D, Petruzzi M, Nowak N, Zabel B, Adam M . Anaplastic Wilms' tumour, a subtype displaying poor prognosis, harbours p53 gene mutations. Nat Genet. 1994; 7(1):91-7. DOI: 10.1038/ng0594-91. View