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The SWI/SNF genetic blockade: effects in cell differentiation, cancer and developmental diseases

Oncogene volume 33, pages 2681–2689 (2014)Cite this article

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Abstract

Our rapidly growing knowledge about cancer genetics attests to the widespread occurrence of alterations at genes encoding different components of the SWI/SNF complex. This reveals an important new feature that sustains cancer development: the blockade of chromatin remodeling. Here, we provide an overview of our current knowledge on the gene alterations of chromatin-remodeling factors, and how they relate to cancer and human developmental diseases. We also consider the functional repercussions, particularly how the inactivation of the SWI/SNF complex impairs the appropriate cell response to nuclear receptor signaling, which, in turn, prevents cell differentiation and sustains cell growth independently of the environment.

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References

  1. Smith CL, Peterson CL . A conserved Swi2/Snf2 ATPase motif couples ATP hydrolysis to chromatin remodeling. Mol Cell Biol 2005; 25: 5880–5892.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Hargreaves DC, Crabtree GR . ATP-dependent chromatin remodeling: genetics, genomics and mechanisms. Cell Res 2011; 21: 396–420.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Lai AY, Wade PA . Cancer biology and NuRD: a multifaceted chromatin remodelling complex. Nat Rev Cancer 2011; 11: 588–596.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Reisman D, Glaros S, Thompson EA . The SWI/SNF complex and cancer. Oncogene 2009; 28: 1653–1668.

    Article  CAS  PubMed  Google Scholar 

  5. Wilson GB . Roberts CWM. SWI/SNF nucleosome remodellers and cancer. Nat Rev Cancer 2011; 11: 281–492.

    Google Scholar 

  6. Versteege I, Sévenet N, Lange J, Rousseau-Merck MF, Ambros P, Handgretinger R et al. Truncating mutations of hSNF5/INI1 in aggressive paediatric cancer. Nature 1998; 394: 203–206.

    Article  CAS  PubMed  Google Scholar 

  7. Sévenet N, Sheridan E, Amram D, Schneider P, Handgretinger R, Delattre O . Constitutional mutations of the hSNF5/INI1 gene predispose to a variety of cancers. Am J Hum Genet 1999; 65: 1342–1348.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Wong AK, Shanahan F, Chen Y, Lian L, Ha P, Hendricks K et al. BRG1, a component of the SWI-SNF complex, is mutated in multiple human tumor cell lines. Cancer Res 2000; 60: 6171–6177.

    CAS  PubMed  Google Scholar 

  9. Medina PP, Romero OA, Kohno T, Montuenga LM, Pio R, Yokota J et al. Frequent BRG1/SMARCA4-inactivating mutations in human lung cancer cell lines. Hum Mut 2008; 29: 617–622.

    Article  CAS  PubMed  Google Scholar 

  10. Medina PP, Carretero J, Fraga MF, Esteller M, Sidransky D, Sanchez-Cespedes M . Genetic and epigenetic screening for gene alterations of the chromatin-remodeling factor, SMARCA4/BRG1, in lung tumors. Genes Chrom Cancer 2004; 41: 170–177.

    Article  CAS  PubMed  Google Scholar 

  11. Rodriguez-Nieto S, Cañada A, Pros E, Pinto AI, Torres-Lanzas J, Lopez-Rios F et al. Massive parallel DNA pyrosequencing analysis of the tumor suppressor BRG1/SMARCA4 in lung primary tumors. Hum Mut 2011; 32: E1999–E2017.

    Article  CAS  PubMed  Google Scholar 

  12. Blanco R, Iwakawa R, Tang M, Kohno T, Angulo B, Pio R et al. A gene-alteration profile of human lung cancer cell lines. Hum Mutat 2009; 30: 1199–1206.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Kiskinis E, García-Pedrero JM, Villaronga MA, Parker MG, Belandia B . Identification of BAF57 mutations in human breast cancer cell lines. Breast Cancer Res Treat 2006; 98: 191–198.

    Article  CAS  PubMed  Google Scholar 

  14. Xia W, Nagase S, Montia AG, Kalachikov SM, Keniry M, Su T et al. BAF180 is a critical regulator of p21 induction and a tumor suppressor mutated in breast cancer. Cancer Res 2008; 68: 1667–1674.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Huang J, Zhao YL, Li Y, Fletcher JA, Xiao S . Genomic and functional evidence for an ARID1A tumor suppressor role. Genes Chrom Cancer 2007; 46: 745–750.

    Article  CAS  PubMed  Google Scholar 

  16. Jones S, Wang TL, IeM Shih, Mao TL, Nakayama K, Roden R et al. Frequent mutations of chromatin remodeling gene ARID1A in ovarian clear cellcarcinoma. Science 2010; 330: 228–231.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Varela I, Tarpey P, Raine K, Huang D, Ong CK, Stephens P et al. Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma. Nature 2011; 469: 539–442.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Gui Y, Guo G, Huang Y, Hu X, Tang A, Gao S et al. Frequent mutations of chromatin remodeling genes in transitional cell carcinoma of the bladder. Nat Genet 2011; 43: 875–878.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Gayther SA, Batley SJ, Linger L, Bannister A, Thorpe K, Chin SF et al. Mutations truncating the EP300 acetylase in human cancers. Nat Genet 2000; 24: 300–303.

    Article  CAS  PubMed  Google Scholar 

  20. Schwartzentruber J, Korshunov A, Liu XY, Jones DT, Pfaff E, Jacob K et al. Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature 2012; 482: 226–231.

    Article  CAS  PubMed  Google Scholar 

  21. Schmitz U, Mueller W, Weber M, Sévenet N, Delattre O, von Deimling A . INI1 mutations in meningiomas at a potential hotspot in exon 9. Br J Cancer 2001; 84: 199–201.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Hulsebos TJ, Plomp AS, Wolterman RA, Robanus-Maandag EC, Baas F, Wesseling P . Germline mutation of INI1/SMARCB1 in familial schwannomatosis. Am J Hum Genet 2007; 80: 805–810.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Roberts CW, Galusha SA, McMenamin ME, Fletcher CD, Orkin SH . Haploinsufficiency of Snf5 (integrase interactor 1) predisposes to malignant rhabdoid tumors in mice. Proc Natl Acad Sci USA 2000; 97: 13796–13800.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Schneppenheim R, Frühwald MC, Gesk S, Hasselblatt M, Jeibmann A, Kordes U et al. Germline nonsense mutation and somatic inactivation of SMARCA4/BRG1 in a family with rhabdoid tumor predisposition syndrome. Am J Hum Genet 2010; 86: 279–284.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Bultman SJ, Gebuhr TC, Magnuson T. A . Brg1 mutation that uncouples ATPase activity from chromatin remodeling reveals an essential role for SWI/SNF-related complexes in beta-globin expression and erythroid development. Genes Dev 2005; 19: 2849–2861.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Bultman SJ, Herschkowitz JI, Godfrey V, Gebuhr TC, Yaniv M, Perou CM et al. Characterization of mammary tumors from Brg1 heterozygous mice. Oncogene 2008; 27: 460–468.

    Article  CAS  PubMed  Google Scholar 

  27. Glaros S, Cirrincione GM, Palanca A, Metzger D, Reisman D . Targeted knockout of BRG1 potentiates lung cancer development. Cancer Res 2008; 68: 3689–3696.

    Article  CAS  PubMed  Google Scholar 

  28. Ko M, Sohn DH, Chung H, Seong RH . Chromatin remodeling, development and disease. Mutat Res 2008; 647: 59–67.

    Article  CAS  PubMed  Google Scholar 

  29. Reyes JC, Barra J, Muchardt C, Camus A, Babinet C, Yaniv M . Altered controlof cellular proliferation in the absence of mammalian brahma (SNF2alpha). EMBO J 1998; 17: 6979–6991.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Halgren C, Kjaergaard S, Bak M, Hansen C, El-Schich Z, Anderson C et al. Corpus callosum abnormalities, intellectual disability, speech impairment, and autism in patients with haploinsufficiency of ARID1B. Clin Genet 2012; 82: 248–255.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Santen GW, Aten E, Sun Y, Almomani R, Gilissen C, Nielsen M et al. Mutations in SWI/SNF chromatin remodeling complex gene ARID1B cause Coffin-Sirissyndrome. Nat Genet 2012; 44: 379–380.

    Article  CAS  PubMed  Google Scholar 

  32. Tsurusaki Y, Okamoto N, Ohashi H, Kosho T, Imai Y, Hibi-Ko Y et al. Mutations affecting components of the SWI/SNF complex cause Coffin-Siris syndrome. Nat Genet 2012; 44: 376–378.

    Article  CAS  PubMed  Google Scholar 

  33. Van Houdt JK, Nowakowska BA, Sousa SB, van Schaik BD, Seuntjens E, Avonce N et al. Heterozygous missense mutations in SMARCA2 cause Nicolaides-Baraitser syndrome. Nat Genet 2012; 44: 445–449.

    Article  CAS  PubMed  Google Scholar 

  34. Wolff D, Endele S, Azzarello-Burri S, Hoyer J, Zweier M, Schanze I et al. In-frame deletion and missense mutations of the C-terminal helicase domain of SMARCA2 in three patients with Nicolaides-Baraitser syndrome. Mol Syndromol 2012; 2: 237–244.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Gibbons RJ, Picketts DJ, Villard L, Higgs DR . Mutations in a putative global transcriptional regulator cause X-linked mental retardation with α-thalassemia (ATR-X syndrome). Cell 1995; 80: 837–845.

    Article  CAS  PubMed  Google Scholar 

  36. Hood RL, Lines MA, Nikkel SM, Schwartzentruber J, Beaulieu C, Nowaczyk MJ et al. Mutations in SRCAP, encoding SNF2-related CREBBP activator protein, cause Floating-Harbor syndrome. Am J Hum Genet 2012; 10: 308–813.

    Article  CAS  Google Scholar 

  37. Kwon CS, Wagner D . Unwinding chromatin for development and growth: a few genes at a time. Trends Genet 2007; 23: 403–412.

    Article  CAS  PubMed  Google Scholar 

  38. Singhal N, Graumann J, Wu G, Arauzo-Bravo MJ, Han DW, Greber B et al. Chromatin-remodeling components of the BAF complex facilitate reprogramming. Cell 2010; 141: 943–955.

    Article  CAS  PubMed  Google Scholar 

  39. de la Serna IL, Carlson KA, Imbalzano AN . Mammalian SWI/SNF complexes promote MyoD-mediated muscle differentiation. Nat Genet 2001; 27: 187–190.

    Article  CAS  PubMed  Google Scholar 

  40. Pedersen TA, Kowenz-Leutz E, Leutz A, Nerlov C . Cooperation betweenC/EBPalpha TBP/TFIIB and SWI/SNF recruiting domains is required for adipocyte differentiation. Genes Dev 2001; 15: 3208–3216.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Gresh L, Bourachot B, Reimann A, Guigas B, Fiette L, Garbay S et al. The SWI/SNF chromatin-remodeling complex subunit SNF5 is essential for hepatocytedifferentiation. EMBO J 2005; 24: 3313–3324.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Matsumoto L, Banine F, Struve J, Xing R, Adams C, Liu Y et al. Brg1 is requiredfor murine neural stem cell maintenance and gliogenesis. Dev Biol 2006; 289: 372–383.

    Article  CAS  PubMed  Google Scholar 

  43. Gebuhr TC, Kovalev GI, Bultman S, Godfrey V, Su L, Magnuson T . The role of Brg1, a catalytic subunit of mammalian chromatin-remodeling complexes, in T cell development. J Exp Med 2003; 198: 1937–1949.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Griffin CT, Brennan J, Magnuson T . The chromatin-remodeling enzyme BRG1 plays an essential role in primitive erythropoiesis and vascular development. Development 2008; 135: 493–500.

    Article  CAS  PubMed  Google Scholar 

  45. Albanese P, Belin MF, Delattre O . The tumour suppressor hSNF5/INI1 controls the differentiation potential of malignant rhabdoid cells. Eur J Cancer 2006; 42: 2326–2334.

    Article  CAS  PubMed  Google Scholar 

  46. Caramel J, Medjkane S, Quignon F, Delattre O . The requirement for SNF5/INI1 in adipocyte differentiation highlights new features of malignant rhabdoid tumors. Oncogene 2008; 27: 2035–2044.

    Article  CAS  PubMed  Google Scholar 

  47. Lickert H, Takeuchi JK, Von Both I, Walls JR, McAuliffe F, Adamson SL et al. Baf60c is essential for function of BAF chromatin remodelling complexes in heart development. Nature 2004; 432: 107–112.

    Article  CAS  PubMed  Google Scholar 

  48. Lamba DA, Hayes S, Karl MO, Reh T . Baf60c is a component of the neural progenitor-specific BAF complex in developing retina. Dev Dyn 2008; 237: 3016–3023.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Forcales SV, Albini S, Giordani L, Malecova B, Cignolo L, Chernov A et al. Signal-dependent incorporation of MyoD-BAF60c into Brg1-based SWI/SNF chromatin-remodelling complex. EMBO J 2011; 31: 301–316.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Wang Y, Wong RH, Tang T, Hudak CS, Yang D, Duncan RE et al. Phosphorylation and recruitment of BAF60c in chromatin remodeling for lipogenesis in response to insulin. Mol Cell 2012; S1097-2765: 00931–00938.

    Google Scholar 

  51. Xu F, Flowers S, Moran E . Essential role of ARID2 protein-containingSWI/SNF complex in tissue-specific gene expression. J Biol Chem 2012; 287: 5033–4501.

    Article  CAS  PubMed  Google Scholar 

  52. Fryer CJ, Archer TK . Chromatin remodelling by the glucocorticoid receptor requires the BRG1 complex. Nature 1998; 393: 88–91.

    Article  CAS  PubMed  Google Scholar 

  53. Chiba H, Muramatsu M, Nomoto A, Kato H . Two human homologues ofSaccharomyces cerevisiae SWI2/SNF2 and Drosophila brahma are transcriptional coactivators cooperating with the estrogen receptor and the retinoic acid receptor. Nucleic Acids Res 1994; 22: 1815–1820.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Debril MB, Gelman L, Fayard E, Annicotte JS, Rocchi S, Auwerx J . Transcription factors and nuclear receptors interact with the SWI/SNF complex through the BAF60c subunit. J Biol Chem 2004; 279: 16677–16686.

    Article  CAS  PubMed  Google Scholar 

  55. Flajollet S, Lefebvre B, Cudejko C, Staels B, Lefebvre P . The core component of the mammalian SWI/SNF complex SMARCD3/BAF60c is a coactivator for the nuclear retinoic acid receptor. Mol Cell Endocrinol 2007; 270: 23–32.

    Article  CAS  PubMed  Google Scholar 

  56. Johnson TA, Elbi C, Parekh BS, Hager GL, John S . Chromatin remodeling complexes interact dynamically with a glucocorticoid receptor-regulated promoter. Mol Biol Cell 2008; 19: 3308–3322.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Biddie SC, Conway-Campbell BL, Lightman SL . Dynamic regulation of glucocorticoid signalling in health and disease. Rheumatology 2012; 51: 403–412.

    Article  CAS  PubMed  Google Scholar 

  58. Siersbæk R, Nielsen R, Mandrup S . Transcriptional networks and chromatin remodeling controlling adipogenesis. Trends Endocrinol Metab 2012; 23: 56–64.

    Article  PubMed  CAS  Google Scholar 

  59. Salma N, Xiao H, Mueller E, Imbalzano AN . Temporal recruitment of transcription factors and SWI/SNF chromatin-remodeling enzymes during adipogenic induction of the peroxisome proliferator-activated receptor gamma nuclear hormone receptor. Mol Cell Biol 2004; 241: 4651–4663.

    Article  CAS  Google Scholar 

  60. Li S, Liu C, Li N, Hao T, Han T, Hill DE et al. Genome-wide coactivation analysis of PGC-1alpha identifies BAF60a as a regulator of hepatic lipid metabolism. Cell Metab 2008; 8: 105–117.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Medina PP, Carretero J, Ballestar E, Angulo B, Lopez-Rios F, Esteller M et al. Transcriptional targets of the chromatin-remodelling factor SMARCA4/BRG1 in lung cancer cells. Hum Mol Genet 2005; 14: 973–982.

    Article  CAS  PubMed  Google Scholar 

  62. Ramirez-Carrozzi VR, Braas D, Bhatt DM, Cheng CS, Hong C, Doty KR et al. A unifying model for the selective regulation of inducible transcription by CpG islands and nucleosome remodeling. Cell 2009; 138: 114–128.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Euskirchen GM, Auerbach RK, Davidov E, Gianoulis TA, Zhong G, Rozowsky J et al. Diverse roles and interactions of the SWI/SNF chromatin remodeling complex revealed using global approaches. PLoS Genet 2011; 7: 3.

    Article  CAS  Google Scholar 

  64. Romero OA, Setien F, John S, Gimenez-Xavier P, Gomez-Lopez G, Pisano D et al. The tumor suppressor BRG1 antagonizes Myc oncogenic activity and promotes cell differentiation in a nuclear receptor-dependent manner. EMBO Mol Med 2012; 4: 603–616.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Wilson BG, Wang X, Shen X, McKenna ES, Lemieux ME, Cho YJ et al. Epigenetic antagonism between polycomb and SWI/SNF complexes during oncogenic transformation. Cancer Cell 2010; 18: 316–328.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Rhinn M, Dollé P . Retinoic acid signalling during development. Development 2012; 139: 843–858.

    Article  CAS  PubMed  Google Scholar 

  67. Kim JK, Huh SO, Choi H, Lee KS, Shin D, Lee C et al. Srg3, a mouse homolog of yeast SWI3, is essential for early embryogenesis and involved in brain development. Mol Cell Biol 2001; 21: 7787–7795.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Saffiotti U, Montesano R, Sellakuma R, Borg SA . Experimental cancer of the lung. Inhibition by vitamin A of the induction of tracheobronchial squamous metaplasia and squamous cell tumors. Cancer 1967; 20: 857–864.

    Article  CAS  PubMed  Google Scholar 

  69. Shi W, Chen F, Cardoso WV . Mechanisms of lung development contribution to adult lung disease and relevance to chronic obstructive pulmonary disease. Proc Am Thorac Soc 2009; 6: 558–563.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Pottier N, Yang W, Assem M, Panetta JC, Pei D, Paugh SW et al. The SWI/SNF chromatin-remodeling complex and glucocorticoid resistance in acute lymphoblastic leukemia. J Natl Cancer Inst 2008; 100: 1792–1803.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Masetti R, Biagi C, Zama D, Vendemini F, Martoni A, Morello W et al. Retinoids in pediatric onco-hematology: the model of acute promyelocytic leukemia and neuroblastoma. Adv Ther 2012; 29: 747–762.

    Article  CAS  PubMed  Google Scholar 

  72. Jung DJ, Lee SK, Lee JW . Agonist-dependent repression mediated by mutant estrogen receptor alpha that lacks the activation function 2 core domain. J Biol Chem 2001; 276: 37280–37283.

    Article  CAS  PubMed  Google Scholar 

  73. Marshall TW, Link KA, Petre-Draviam CE, Knudsen KE . Differential requirementof SWI/SNF for androgen receptor activity. J Biol Chem 2003; 278: 30605–30613.

    Article  CAS  PubMed  Google Scholar 

  74. García-Pedrero JM, Kiskinis E, Parker MG, Belandia B . The SWI/SNF chromatin remodeling subunit BAF57 is a critical regulator of estrogen receptor function in breast cancer cells. J Biol Chem 2006; 281: 22656–22664.

    Article  PubMed  CAS  Google Scholar 

  75. Hendricks KB, Shanahan F, Lees E . Role for BRG1 in cell cycle control and tumor suppression. Mol Cell Biol 2004; 24: 362–376.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Chai B, Huang J, Cairns BR, Laurent BC . Distinct roles for the RSC and Swi/Snf ATP-dependent chromatin remodelers in DNA double-strand break repair. Genes Dev 2005; 19: 1656–1661.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Pal S, Yun R, Datta A, Lacomis L, Erdjument-Bromage H, Kumar J et al. mSin3A/histone deacetylase 2- and PRMT5-containing Brg1 complex is involved in transcriptional repression of the Myc target gene cad. Mol Cell Biol 2003; 23: 7475–7487.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Zhang Y, Sif S, DeWille J . The mouse C/EBPdelta gene promoter is regulated by STAT3 and Sp1 transcriptional activators, chromatin remodeling and c-Myc repression. J Cell Biochem 2007; 102: 1256–1270.

    Article  CAS  PubMed  Google Scholar 

  79. Geradts J, Chen JY, Russell EK, Yankaskas JR, Nieves L, Minna JD . Human lung cancer cell lines exhibit resistance to retinoic acid treatment. Cell Growth Differ 1993; 4: 799–809.

    CAS  PubMed  Google Scholar 

  80. Biegel JA, Zhou JY, Rorke LB, Stenstrom C, Wainwright LM, Fogelgren B . Germ-line and acquired mutations of INI1 in atypical teratoid and rhabdoid tumors. Cancer Res 1999; 59: 74–79.

    CAS  PubMed  Google Scholar 

  81. Shain AH, Giacomini CP, Matsukuma K, Karikari CA, Bashyam MD, Hidalgo M et al. Convergent structural alterations define SWItch/Sucrose NonFermentable (SWI/SNF) chromatin remodeler as a central tumor suppressive complex in pancreatic cancer. Proc Natl Acad Sci USA 2012; 109: E252–E259.

    Article  CAS  PubMed  Google Scholar 

  82. Parsons DW, Li M, Zhang X, Jones S, Leary RJ, Lin JC et al. The genetic landscape of the childhood cancer medulloblastoma. Science 2011; 331: 435–439.

    Article  CAS  PubMed  Google Scholar 

  83. Jones DT, Jäger N, Kool M, Zichner T, Hutter B, Sultan M et al. Dissectingthe genomic complexity underlying medulloblastoma. Nature 2012; 488: 100–105.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Pugh TJ, Weeraratne SD, Archer TC, Pomeranz Krummel DA, Auclair D, Bochicchio J et al. Medulloblastoma exome sequencing uncovers subtype-specific somatic mutations. Nature 2012; 488: 106–110.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Love C, Sun Z, Jima D, Li G, Zhang J, Miles R et al. The genetic landscape of mutations in Burkitt lymphoma. Nat Genet 2012; 44: 1321–1325.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Hasselblatt M, Gesk S, Oyen F, Rossi S, Viscardi E, Giangaspero F et al. Nonsense mutation and inactivation of SMARCA4 (BRG1) in an atypical teratoid/rhabdoid tumor showing retained SMARCB1 (INI1) expression. Am J Surg Pathol 2011; 35: 933–935.

    Article  PubMed  Google Scholar 

  87. Xu X, Hou Y, Yin X, Bao L, Tang A, Song L et al. Single-cell exome sequencing reveals single-nucleotide mutation characteristics of a kidney tumor. Cell 2012; 148: 886–895.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Wang K, Kan J, Yuen ST, Shi ST, Chu KM, Law S et al. Exome sequencing identifies frequent mutation of ARID1A in molecular subtypes of gastric cancer. Nat Genet 2011; 43: 1219–1223.

    Article  CAS  PubMed  Google Scholar 

  89. Mamo A, Cavallone L, Tuzmen S, Chabot C, Ferrario C, Hassan S et al. An integrated genomic approach identifies ARID1A as a candidate tumor-suppressor gene in breast cancer. Oncogene 2012; 31: 2090–2100.

    Article  CAS  PubMed  Google Scholar 

  90. Imielinski M, Berger AH, Hammerman PS, Hernandez B, Pugh TJ, Hodis E et al. Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing. Cell 2012; 150: 1107–1120.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Wiegand KC, Shah SP, Al-Agha OM, Zhao Y, Tse K, Zeng T et al. ARID1Amutations in endometriosis-associated ovarian carcinomas. N Engl J Med 2010; 363: 1532–1543.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Guan B, Wang TL, Shih IM . ARID1A, a factor that promotes formation ofSWI/SNF-mediated chromatin remodeling, is a tumor suppressor in gynecologic cancers. Cancer Res 2011; 71: 6718–6727.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Le Gallo M, O’Hara AJ, Rudd ML, Urick ME, Hansen NF, O'Neil NJ et al. Exome sequencing of serous endometrial tumors identifies recurrent somatic mutations in chromatin-remodeling and ubiquitin ligase complex genes. Nat Genet 2012; 44: 1310–1315.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Giulino-Roth L, Wang K, Macdonald TY, Mathew S, Tam Y, Cronin MT et al. Targeted genomic sequencing of pediatric Burkitt lymphoma identifies recurrent alterations in antiapoptotic and chromatin-remodeling genes. Blood 2012; 120: 5181–5184.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Sausen M, Leary RJ, Jones S, Wu J, Reynolds CP, Liu X et al. Integrated genomic analyses identify ARID1A and ARID1B alterations in the childhood cancerneuroblastoma. Nat Genet 2012; 45: 12–17.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  96. Biankin AV, Waddell N, Kassahn KS, Gingras MC, Muthuswamy LB, Johns AL et al. Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes. Nature 2012; 491: 399–405.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Fujimoto A, Totoki Y, Abe T, Boroevich KA, Hosoda F, Nguyen HH et al. Whole-genome sequencing of liver cancers identifies etiological influences on mutation patterns and recurrent mutations in chromatin regulators. Nat Genet 2012; 44: 760–764.

    Article  CAS  PubMed  Google Scholar 

  98. Guichard C, Amaddeo G, Imbeaud S, Ladeiro Y, Pelletier L, Maad IB et al. Integrated analysis of somatic mutations and focal copy-number changes identifies key genes and pathways in hepatocellular carcinoma. Nat Genet 2012; 44: 694–698.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Huang J, Deng Q, Wang Q, Li KY, Dai JH, Li N et al. Exome sequencing ofhepatitis B virus-associated hepatocellular carcinoma. Nat Genet 2012; 44: 1117–1121.

    Article  CAS  PubMed  Google Scholar 

  100. Manceau G, Letouzé E, Guichard C, Didelot A, Cazes A, Corté H et al. Recurrent inactivating mutations of ARID2 in non-small cell lung carcinoma. Int J Cancer 2012; 132: 2217–2221.

    Article  PubMed  CAS  Google Scholar 

  101. DelBove J, Rosson G, Strobeck M, Chen J, Archer TK, Wang W et al. Identification of a core member of the SWI/SNF complex, BAF155/SMARCC1, as a human tumor suppressor gene. Epigenetics 2011; 6: 1444–1453.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Stephens PJ, Tarpey PS, Davies H, Van Loo P, Greenman C, Wedge DC et al. Oslo Breast Cancer Consortium (OSBREAC) The landscape of cancer genes and mutational processes in breast cancer. Nature 2012; 486: 400–404.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Wang Z, Zhai W, Richardson JA, Olson EN, Meneses JJ, Firpo MT et al. Polybromo protein BAF180 functions in mammalian cardiac chamber maturation. Genes Dev 2004; 18: 3106–3116.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Wu JI, Lessard J, Olave IA, Qiu Z, Ghosh A, Graef IA et al. Regulation of dendritic development by neuron-specific chromatin remodeling complexes. Neuron 2007; 56: 94–108.

    Article  CAS  PubMed  Google Scholar 

  105. Smith MJ, O’Sullivan J, Bhaskar SS, Hadfield KD, Poke G, Caird J et al. Loss-of-function mutations in SMARCE1 cause an inherited disorder of multiple spinal meningiomas. Nat Genet 2013; 45: 295–298.

    Article  CAS  PubMed  Google Scholar 

  106. Hoyer J, Ekici AB, Endele S, Popp B, Zweier C, Wiesener A et al. Haploinsufficiency of ARID1B, a member of the SWI/SNF-a chromatin-remodeling complex,is a frequent cause of intellectual disability. Am J Hum Genet 2012; 90: 565–572.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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  1. Genes and Cancer Group, Cancer Epigenetics and Biology Program—PEBC, Bellvitge Biomedical Research Institute—IDIBELL, Hospitalet de Llobregat, Barcelona, Spain

    O A Romero & M Sanchez-Cespedes

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  1. O A Romero
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  2. M Sanchez-Cespedes
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Correspondence to M Sanchez-Cespedes.

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Romero, O., Sanchez-Cespedes, M. The SWI/SNF genetic blockade: effects in cell differentiation, cancer and developmental diseases. Oncogene 33, 2681–2689 (2014). https://doi.org/10.1038/onc.2013.227

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  • DOI: https://doi.org/10.1038/onc.2013.227

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