Medulloblastomics: The end of the beginning

Nature Reviews Cancer

Volumn 12, Issue 12, 2012, Pages 818-834

  Northcott, Paul A ^a   Jones, David T W ^a   Kool, Marcel ^a   Robinson, Giles W ^b   Gilbertson, Richard J ^b   Cho, Yoon Jae ^c   Pomeroy, Scott L ^d,e   Korshunov, Andrey ^a   Lichter, Peter ^a   Taylor, Michael D ^f,g   Pfister, Stefan M ^a,h  

^a GERMAN CANCER RESEARCH CENTER DKFZ   (Germany)

^b ST JUDE CHILDREN S RESEARCH HOSPITAL   (United States)

^c STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d BOSTON CHILDREN S HOSPITAL   (United States)

^e BROAD INSTITUTE OF MIT AND HARVARD   (United States)

^f HOSPITAL FOR SICK CHILDREN   (Canada)

^g UNIVERSITY OF TORONTO   (Canada)

^h UNIVERSITY HOSPITAL HEIDELBERG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

SONIC HEDGEHOG PROTEIN; WNT PROTEIN;

CANCER PROGNOSIS; CANCER RECURRENCE; DISEASE PREDISPOSITION; DISEASE SEVERITY; GENE DUPLICATION; GENE EXPRESSION; GENE MUTATION; GENETIC CODE; GENETIC SUSCEPTIBILITY; GENOMICS; GENOTYPE; HETEROZYGOTE; HISTONE MODIFICATION; HUMAN; MEDULLOBLASTOMA; MICROARRAY ANALYSIS; MOLECULARLY TARGETED THERAPY; MUTATIONAL ANALYSIS; NONHUMAN; OVERALL SURVIVAL; PHENOTYPE; PRIORITY JOURNAL; REVIEW; SEQUENCE ANALYSIS; TETRAPLOIDY; TUMOR GENE;

ANIMALS; BETA CATENIN; CEREBELLAR NEOPLASMS; CHILD; CYCLIN-DEPENDENT KINASE 6; DNA MUTATIONAL ANALYSIS; FEMALE; GENOME-WIDE ASSOCIATION STUDY; GENOMICS; HEDGEHOG PROTEINS; HISTONES; HUMANS; MALE; MEDULLOBLASTOMA; MICE; MUTATION; SIGNAL TRANSDUCTION; TETRAPLOIDY;

EID: 84870215426     PISSN: 1474175X     EISSN: 14741768     Source Type: Journal    
DOI: 10.1038/nrc3410     Document Type: Review

References (110)

1. Pui, C. H., Gajjar, A. J., Kane, J. R., Qaddoumi, I. A. & Pappo, A. S. Challenging issues in pediatric oncology. Nature Rev. Clin. Oncol. 8, 540-549 (2011
2. Siegel, R., Naishadham, D. & Jemal, A. Cancer statistics, 2012. CA Cancer J. Clin. 62, 10-29 (2012
3. Gajjar, A. et al. Risk-adapted craniospinal radiotherapy followed by high-dose chemotherapy and stem-cell rescue in children with newly diagnosed medulloblastoma (St. Jude Medulloblastoma 96): long-term results from a prospective, multicentre trial. Lancet Oncol. 7, 813-820 (2006 (Pubitemid 44464063)
4. Rutkowski, S. et al. Survival and prognostic factors of early childhood medulloblastoma: an international meta-analysis. J. Clin. Oncol. 28, 4961-4968 (2010
5. Ellison, D. W. et al. ß-Catenin status predicts a favorable outcome in childhood medulloblastoma: the United Kingdom Children's Cancer Study Group Brain Tumour Committee. J. Clin. Oncol. 23, 7951-7957 (2005). This study was the first to show that CTNNB1 mutated medulloblastomas, which would subsequently define the WNT subgroup, have an excellent prognosis compared with non-CTNNB1-mutated cases. (Pubitemid 46657395)
6. This study was the first to show that CTNNB1 mutated medulloblastomas, which would subsequently define the WNT subgroup, have an excellent prognosis compared with non-CTNNB1-mutated cases. 6. Packer, R. J. & Vezina, G. Management of and prognosis with medulloblastoma: therapy at a crossroads. Arch. Neurol. 65, 1419-1424 (2008
7. Mabbott, D. J., Penkman, L., Witol, A., Strother, D. & Bouffet, E. Core neurocognitive functions in children treated for posterior fossa tumors. Neuropsychology 22, 159-168 (2008 (Pubitemid 351626504)
8. Mabbott, D. J. et al. Serial evaluation of academic and behavioral outcome after treatment with cranial radiation in childhood. J. Clin. Oncol. 23, 2256-2263 (2005 (Pubitemid 46218718)
9. Spiegler, B. J., Bouffet, E., Greenberg, M. L., Rutka, J. T. & Mabbott, D. J. Change in neurocognitive functioning after treatment with cranial radiation in childhood. J. Clin. Oncol. 22, 706-713 (2004 (Pubitemid 41095075)
10. Low, J. A. & de Sauvage, F. J. Clinical experience with Hedgehog pathway inhibitors. J. Clin. Oncol. 28, 5321-5326 (2010
11. Ng, J. M. & Curran, T. The Hedgehog's tale: developing strategies for targeting cancer. Nature Rev. Cancer 11, 493-501 (2011
12. Taylor, M. D., Mainprize, T. G. & Rutka, J. T. Molecular insight into medulloblastoma and central nervous system primitive neuroectodermal tumor biology from hereditary syndromes: a review. Neurosurgery 47, 888-901 (2000 (Pubitemid 32103665)
13. Hahn, H. et al. Mutations of the human homolog of Drosophila patched in the nevoid basal cell carcinoma syndrome. Cell 85, 841-851 (1996 (Pubitemid 26192135)
14. Johnson, R. L. et al. Human homolog of patched, a candidate gene for the basal cell nevus syndrome. Science 272, 1668-1671 (1996). References 13 and 14 implicated mutations in PTCH1 as the underlying cause of Gorlin syndrome. (Pubitemid 26200029)
15. References 13 and 14 implicated mutations in PTCH1 as the underlying cause of Gorlin syndrome. 15. Gailani, M. R. et al. Developmental defects in Gorlin syndrome related to a putative tumor suppressor gene on chromosome 9. Cell 69, 111-117 (1992
16. Raffel, C. et al. Sporadic medulloblastomas contain PTCH mutations. Cancer Res. 57, 842-845 (1997 (Pubitemid 27098006)
17. Pietsch, T. et al. Medulloblastomas of the desmoplastic variant carry mutations of the human homologue of Drosophila patched. Cancer Res. 57, 2085-2088 (1997 (Pubitemid 27247016)
18. Wolter, M., Reifenberger, J., Sommer, C., Ruzicka, T. & Reifenberger, G. Mutations in the human homologue of the Drosophila segment polarity gene patched (PTCH) in sporadic basal cell carcinomas of the skin and primitive neuroectodermal tumors of the central nervous system. Cancer Res. 57, 2581-2585 (1997 (Pubitemid 27283761)
19. Kool, M. et al. Molecular subgroups of medulloblastoma: an international meta-analysis of transcriptome, genetic aberrations, and clinical data of WNT, SHH, Group 3, and Group 4 medulloblastomas. Acta Neuropathol. 123, 473-484 (2012). This study combined all published genomic data of medulloblastomas and effectivley summarized the main clinical and genomic features defining the medulloblastoma subgroups.
20. This study combined all published genomic data of medulloblastomas and effectivley summarized the main clinical and genomic features defining the medulloblastoma subgroups. 20. Hamilton, S. R. et al. The molecular basis of Turcot's syndrome. New Engl. J. Med. 332, 839-847 (1995
21. Zurawel, R. H., Chiappa, S. A., Allen, C. & Raffel, C. Sporadic medulloblastomas contain oncogenic ß-catenin mutations. Cancer Res. 58, 896-899 (1998 (Pubitemid 28182454)
22. Eberhart, C. G., Tihan, T. & Burger, P. C. Nuclear localization and mutation of ß-catenin in medulloblastomas. J. Neuropathol. Exp. Neurol. 59, 333-337 (2000 (Pubitemid 30183701)
23. Pastorino, L. et al. Identification of a SUFU germline mutation in a family with Gorlin syndrome. Am. J. Med. Genet. A 149A, 1539-1543 (2009
24. Taylor, M. D. et al. Mutations in SUFU predispose to medulloblastoma. Nature Genet. 31, 306-310 (2002). This study identified germline and somatic mutations of SUFU in patients with medulloblastoma, establishing it as an important TSG in the SHH pathway.
25. Dahmen, R. P. et al. Deletions of AXIN1, a component of the WNT/wingless pathway, in sporadic medulloblastomas. Cancer Res. 61, 7039-7043 (2001 (Pubitemid 32946492)
26. Baeza, N., Masuoka, J., Kleihues, P. & Ohgaki, H. AXIN1 mutations but not deletions in cerebellar medulloblastomas. Oncogene 22, 632-636 (2003 (Pubitemid 36188620)
27. Smyth, I. et al. Isolation and characterization of human patched 2 (PTCH2), a putative tumour suppressor gene inbasal cell carcinoma and medulloblastoma on chromosome 1p32. Hum. Mol. Genet. 8, 291-297 (1999 (Pubitemid 29054270)
28. Koch, A. et al. Mutations of the Wnt antagonist AXIN2 (Conductin) result in TCF-dependent transcription in medulloblastomas. Int. J. Cancer 121, 284-291 (2007 (Pubitemid 46917696)
29. Lam, C. W. et al. A frequent activated smoothened mutation in sporadic basal cell carcinomas. Oncogene 18, 833-836 (1999
30. Meyerson, M., Gabriel, S. & Getz, G. Advances in understanding cancer genomes through second-generation sequencing. Nature Rev. Genet. 11, 685-696 (2010
31. Stratton, M. R. Exploring the genomes of cancer cells: progress and promise. Science 331, 1553-1558 (2011
32. Robinson, G. et al. Novel mutations target distinct subgroups of medulloblastoma. Nature 488, 43-48 (2012
33. Jones, D. T. et al. Dissecting the genomic complexity underlying medulloblastoma. Nature 488,100-105 (2012
34. Pugh, T. J. et al. Medulloblastoma exome sequencing uncovers subtype-specific somatic mutations. Nature 488, 106-110 (2012). References 32 to 34 were the first studies to apply next-generation sequencing to large cohorts of medulloblastoma samples in order to catalogue the prevalent somatic mutations in the disease. 35. Rausch,
35. Rausch, T. et al. Genome sequencing of pediatric medulloblastoma links catastrophic DNA rearrangements with TP53 mutations. Cell 148, 59-71 (2012). This study used WGS to describe the genomic landscape of medulloblastomas arising in patients with LFS, uncovering chromothripsis as a signature event in this subset of patients.
36. Northcott, P. A. et al. The miR 17/92 polycistron is up regulated in sonic hedgehog-driven medulloblastomas and induced by N myc in sonic hedgehog-treated cerebellar neural precursors. Cancer Res. 69, 3249-3255 (2009
37. Thompson, M. C. et al. Genomics identifies medulloblastoma subgroups that are enriched for specific genetic alterations. J. Clin. Oncol. 24, 1924-1931 (2006 (Pubitemid 46638992)
38. Kool, M. et al. Integrated genomics identifies five medulloblastoma subtypes with distinct genetic profiles, pathway signatures and clinicopathological features. PLoS ONE 3, e3088 (2008). References 37 and 38 were the first to report the existence of distinct molecular subgroups of medulloblastoma based on unsupervised analyses of transcriptional profiles.
39. Cho, Y. J. et al. Integrative genomic analysis of medulloblastoma identifies a molecular subgroup that drives poor clinical outcome. J. Clin. Oncol. 29, 1424-1430 (2011
40. Northcott, P. A. et al. Medulloblastoma comprises four distinct molecular variants. J. Clin. Oncol. 29, 1408-1414 (2011). References 39 and 40 are highly complementary studies on the genomic and clinical characteristics of medulloblastoma subgroups and instigated the definition of the currently recognized consensus subgroups.
41. Remke, M. et al. FSTL5 is a marker of poor prognosis in non-WNT/non-SHH medulloblastoma. J. Clin. Oncol. 29, 3852-3861 (2011
42. Taylor, M. D. et al. Molecular subgroups of medulloblastoma: the current consensus. Acta Neuropathol. 123, 465-472 (2012). This report is the consensus statement on the four subgroup structure of medulloblastoma agreed on by the medulloblastoma community.
43. Northcott, P. A., Korshunov, A., Pfister, S. M. & Taylor, M. D. The clinical implications of medulloblastoma subgroups. Nature Rev. Neurol. 8, 340-351 (2012
44. Northcott, P. A., Dubuc, A. M., Pfister, S. & Taylor, M. D. Molecular subgroups of medulloblastoma. Expert Rev. Neurother. 12, 871-884 (2012
45. Packer, R. J. Risk stratification of medulloblastoma: a paradigm for future childhood brain tumor management strategies. Curr. Neurol. Neurosci. Rep. 11, 124-126 (2011
46. Leary, S. E. & Olson, J. M. The molecular classification of medulloblastoma: driving the next generation clinical trials. Curr. Opin. Pediatr. 24, 33-39 (2012
47. Pomeroy, S. L. et al. Prediction of central nervous system embryonal tumour outcome based on gene expression. Nature 415, 436-442 (2002). This study used gene expression array profiling to discriminate different histologies of paediatric brain tumours and provided definitive molecular evidence of medulloblastoma as being distinct from other primitive neuroectodermal tumours. (Pubitemid 34100955)
48. Clifford, S. C. et al. Wnt/Wingless pathway activation and chromosome 6 loss characterize a distinct molecular sub-group of medulloblastomas associated with a favorable prognosis. Cell Cycle 5, 2666-2670 (2006
49. Pfaff, E. et al. TP53 mutation is frequently associated with CTNNB1 mutation or MYCN amplification and is compatible with long-term survival in medulloblastoma. J. Clin. Oncol. 28, 5188-5196 (2010
50. Lindsey, J. C. et al. TP53 mutations in favorable-risk Wnt/Wingless-subtype medulloblastomas. J. Clin. Oncol. 29, e344-e348 (2011
51. Northcott, P. A. et al. Rapid, reliable, and reproducible molecular sub-grouping of clinical medulloblastoma samples. Acta Neuropathol. 123, 615-626 (2012
52. Gibson, P. et al. Subtypes of medulloblastoma have distinct developmental origins. Nature 468, 1095-1099 (2010). This study described the first mouse model to faithfully recapitulate human WNT medulloblastoma and proposed LRPs as their putative cell of origin.
53. Northcott, P. A. et al. Pediatric and adult sonic hedgehog medulloblastomas are clinically and molecularly distinct. Acta Neuropathol. 122, 231-240 (2011
54. Ellison, D. W. et al. Medulloblastoma: clinicopathological correlates of SHH, WNT, and non-SHH/WNT molecular subgroups. Acta Neuropathol. 121, 381-396 (2011
55. Brugieres, L. et al. High frequency of germline SUFU mutations in children with desmoplastic/nodular medulloblastoma younger than 3 years of age. J. Clin. Oncol. 30, 2087-2093 (2012
56. Brugieres, L. et al. Incomplete penetrance of the predisposition to medulloblastoma associated with germ-line SUFU mutations. J. Med. Genet. 47, 142-144 (2010
57. Garre, M. L. et al. Medulloblastoma variants: age-dependent occurrence and relation to Gorlin syndrome-a new clinical perspective. Clin. Cancer Res. 15, 2463-2471 (2009
58. Huse, J. T. & Holland, E. C. Genetically engineered mouse models of brain cancer and the promise of preclinical testing. Brain Pathol. 19, 132-143 (2009
59. Wu, X., Northcott, P. A., Croul, S. & Taylor, M. D. Mouse models of medulloblastoma. Chin. J. Cancer 30, 442-449 (2011
60. Goodrich, L. V., Milenkovic, L., Higgins, K. M. & Scott, M. P. Altered neural cell fates and medulloblastoma in mouse patched mutants. Science 277, 1109-1113 (1997). This article introduced the first sporadic mouse model of medulloblastoma generated through germline deletion of one allele of the Ptch1 TSG. (Pubitemid 27371635)
61. Wetmore, C., Eberhart, D. E. & Curran, T. The normal patched allele is expressed in medulloblastomas from mice with heterozygous germ-line mutation of patched. Cancer Res. 60, 2239-2246 (2000 (Pubitemid 30225189)
62. Hatton, B. A. et al. The Smo/Smo model: hedgehog-induced medulloblastoma with 90% incidence and leptomeningeal spread. Cancer Res. 68, 1768-1776 (2008 (Pubitemid 351416562)
63. Hallahan, A. R. et al. The SmoA1 mouse model reveals that notch signaling is critical for the growth and survival of sonic hedgehog-induced medulloblastomas. Cancer Res. 64, 7794-7800 (2004 (Pubitemid 39446912)
64. Oliver, T. G. et al. Loss of patched and disruption of granule cell development in a pre-neoplastic stage of medulloblastoma. Development 132, 2425-2439 (2005 (Pubitemid 40872811)
65. Yang, Z. J. et al. Medulloblastoma can be initiated by deletion of Patched in lineage-restricted progenitors or stem cells. Cancer Cell 14, 135-145 (2008
66. Schuller, U. et al. Acquisition of granule neuron precursor identity is a critical determinant of progenitor cell competence to form Shh-induced medulloblastoma. Cancer Cell 14, 123-134 (2008
67. Grammel, D. et al. Sonic hedgehog-associated medulloblastoma arising from the cochlear nuclei of the brainstem. Acta Neuropathol. 123, 601-614 (2012
68. Rudin, C. M. et al. Treatment of medulloblastoma with hedgehog pathway inhibitor GDC 0449. New Engl. J. Med. 361, 1173-1178 (2009). This study demonstrated proof of principle for targeted therapy of medulloblastoma through administration of a pharmacological inhibitor of SMO to a single patient with metastatic medulloblastoma, resulting in a profound but transient response and subsequent therapeutic resistance.
69. Yauch, R. L. et al. Smoothened mutation confers resistance to a Hedgehog pathway inhibitor in medulloblastoma. Science 326, 572-574 (2009
70. Buonamici, S. et al. Interfering with resistance to smoothened antagonists by inhibition of the PI3K pathway in medulloblastoma. Sci. Transl. Med. 2, 51ra70 (2010
71. Dijkgraaf, G. J. et al. Small molecule inhibition of GDC 0449 refractory smoothened mutants and downstream mechanisms of drug resistance. Cancer Res. 71, 435-444 (2011
72. Metcalfe, C. & de Sauvage, F. J. Hedgehog fights back: mechanisms of acquired resistance against Smoothened antagonists. Cancer Res. 71, 5057-5061 (2011
73. Northcott, P. A. et al. Multiple recurrent genetic events converge on control of histone lysine methylation in medulloblastoma. Nature Genet. 41, 465-472 (2009). This study used SNP arrays to identify significant copy number aberrations in the medulloblastoma genome and was the first to implicate deregulation of chromatin modifiers as an important theme in medulloblastoma biology.
74. Kimura, H., Ng, J. M. & Curran, T. Transient inhibition of the Hedgehog pathway in young mice causes permanent defects in bone structure. Cancer Cell 13, 249-260 (2008 (Pubitemid 351324879)
75. Pei, Y. et al. An animal model of MYC-driven medulloblastoma. Cancer Cell 21, 155-167 (2012
76. Kawauchi, D. et al. A mouse model of the most aggressive subgroup of human medulloblastoma. Cancer Cell 21, 168-180 (2012). References 75 and 76 describe the successful generation of in vivo models of MYC-driven Group 3 medulloblastoma.
77. References 75 and 76 describe the successful generation of in vivo models of MYC-driven Group 3 medulloblastoma. 77. Remke, M. et al. Adult medulloblastoma comprises three major molecular variants. J. Clin. Oncol. 29, 2717-2723 (2011
78. Eberhart, C. G. Three down and one to go: modeling medulloblastoma subgroups. Cancer Cell 21, 137-138 (2012
79. Swartling, F. J. et al. Distinct neural stem cell populations give rise to disparate brain tumors in response to N MYC. Cancer Cell 21, 601-613 (2012
80. Swartling, F. J. et al. Pleiotropic role for MYCN in medulloblastoma. Genes Dev. 24, 1059-1072 (2010). This article introduced an elegant mouse model of MYCN-driven medulloblastoma relying on a bidirectional transgenic promoter expressing both MYCN and luciferase in the developing mouse cerebellum that generated highly penetrant mouse medulloblastomas with similar features of the human disease.
81. Northcott, P. A., Rutka, J. T. & Taylor, M. D. Genomics of medulloblastoma: from Giemsa-banding to next-generation sequencing in 20 years. Neurosurg. Focus 28, e6 (2010
82. Ciara, E. et al. Heterozygous germ-line mutations in the NBN gene predispose to medulloblastoma in pediatric patients. Acta Neuropathol. 119, 325-334 (2010
83. Distel, L., Neubauer, S., Varon, R., Holter, W. & Grabenbauer, G. Fatal toxicity following radio- and chemotherapy of medulloblastoma in a child with unrecognized Nijmegen breakage syndrome. Med. Pediatr. Oncol. 41, 44-48 (2003 (Pubitemid 41103253)
84. Taylor, M. D. et al. Medulloblastoma in a child with Rubenstein-Taybi Syndrome: case report and review of the literature. Pediatr. Neurosurg. 35, 235-238 (2001 (Pubitemid 34008796)
85. Parsons, D. W. et al. The genetic landscape of the childhood cancer medulloblastoma. Science 331, 435-439 (2011). This study was the first unbiased exome-wide sequencing study of medulloblastoma and identified novel recurrent somatic mutations in the chromatin modifiers MLL2 and MLL3.
86. Parsons, D. W. et al. An integrated genomic analysis of human glioblastoma multiforme. Science 321, 1807-1812 (2008
87. Hodis, E. et al. A landscape of driver mutations in melanoma. Cell 150, 251-263 (2012
88. Banerji, S. et al. Sequence analysis of mutations and translocations across breast cancer subtypes. Nature 486, 405-409 (2012
89. Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma. Nature 474, 609-615 (2011
90. Cancer Genome Atlas Research Network. Comprehensive molecular characterization of human colon and rectal cancer. Nature 487, 330-337 (2012
91. Barbieri, C. E. et al. Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer. Nature Genet. 44, 685-689 (2012
92. Pek, J. W. & Kai, T. DEAD-box RNA helicase Belle/DDX3 and the RNA interference pathway promote mitotic chromosome segregation. Proc. Natl Acad. Sci. USA 108, 12007-12012 (2011
93. Lai, M. C., Chang, W. C., Shieh, S. Y. & Tarn, W. Y. DDX3 regulates cell growth through translational control of cyclin E1. Mol. Cell. Biol. 30, 5444-5453 (2010
94. Schroder, M. Human DEAD-box protein 3 has multiple functions in gene regulation and cell cycle control and is a prime target for viral manipulation. Biochem. Pharmacol. 79, 297-306 (2010
95. Lee, C. S. et al. Human DDX3 functions in translation and interacts with the translation initiation factor eIF3. Nucleic Acids Res. 36, 4708-4718 (2008
96. Lai, M. C., Lee, Y. H. & Tarn, W. Y. The DEAD-box RNA helicase DDX3 associates with export messenger ribonucleoproteins as well as tip-associated protein and participates in translational control. Mol. Biol. Cell 19, 3847-3858 (2008
97. Rosner, A. & Rinkevich, B. The DDX3 subfamily of the DEAD box helicases: divergent roles as unveiled by studying different organisms and in vitro assays. Curr. Med. Chem. 14, 2517-2525 (2007 (Pubitemid 47618039)
98. Hogbom, M. et al. Crystal structure of conserved domains 1 and 2 of the human DEAD-box helicase DDX3X in complex with the mononucleotide AMP. J. Mol. Biol. 372, 150-159 (2007 (Pubitemid 47241140)
99. Northcott, P. A. et al. Subgroup-specific structural variation across 1,000 medulloblastoma genomes. Nature 488, 49-56 (2012). This study described the SCNAs present in a series of >1,000 primary medulloblastomas and led to the discovery of several novel medulloblastoma subgroup-specific alterations, including PVT1-MYC fusion genes in Group 3 medulloblastoma and tandem duplication of SNCAIP in Group 4 medulloblastoma.
100. Sengoku, T. & Yokoyama, S. Structural basis for histone H3 Lys 27 demethylation by UTX/KDM6A. Genes Dev. 25, 2266-2277 (2011
101. Kim, E. & Song, J. J. Diverse ways to be specific: a novel Zn binding domain confers substrate specificity to UTX/KDM6A histone H3 Lys 27 demethylase. Genes Dev. 25, 2223-2226 (2011
102. Kooistra, S. M. & Helin, K. Molecular mechanisms and potential functions of histone demethylases. Nature Rev. Mol. Cell Biol. 13, 297-311 (2012
103. Lee, M. G., Wynder, C., Cooch, N. & Shiekhattar, R. An essential role for CoREST in nucleosomal histone 3 lysine 4 demethylation. Nature 437, 432-435 (2005 (Pubitemid 41613507)
104. Schnetz, M. P. et al. CHD7 targets active gene enhancer elements to modulate ES cell-specific gene expression. PLoS Genet. 6, e1001023 (2010
105. Bajpai, R. et al. CHD7 cooperates with PBAF to control multipotent neural crest formation. Nature 463, 958-962 (2010
106. Schnetz, M. P. et al. Genomic distribution of CHD7 on chromatin tracks H3K4 methylation patterns. Genome Res. 19, 590-601 (2009
107. Greer, E. L. & Shi, Y. Histone methylation: a dynamic mark in health, disease and inheritance. Nature Rev. Genet. 13, 343-357 (2012
108. Margueron, R. & Reinberg, D. The Polycomb complex PRC2 and its mark in life. Nature 469, 343-349 (2011
109. Alimova, I. et al. Targeting the enhancer of zeste homologue 2 in medulloblastoma. International journal of cancer. J. Inter. Cancer 131,1800-1809 (2012
110. Oberoi, J. et al. Structural basis for the assembly of the SMRT/NCoR core transcriptional repression machinery. Nature Struct. Mol. Biol. 18, 177-184 (2011).