Ontology type: schema:ScholarlyArticle Open Access: True
2013-03
AUTHORSAdrian M. Dubuc, Marc Remke, Andrey Korshunov, Paul A. Northcott, Shing H. Zhan, Maria Mendez-Lago, Marcel Kool, David T. W. Jones, Alexander Unterberger, A. Sorana Morrissy, David Shih, John Peacock, Vijay Ramaswamy, Adi Rolider, Xin Wang, Hendrik Witt, Thomas Hielscher, Cynthia Hawkins, Rajeev Vibhakar, Sidney Croul, James T. Rutka, William A. Weiss, Steven J. M. Jones, Charles G. Eberhart, Marco A. Marra, Stefan M. Pfister, Michael D. Taylor
ABSTRACTRecent sequencing efforts have described the mutational landscape of the pediatric brain tumor medulloblastoma. Although MLL2 is among the most frequent somatic single nucleotide variants (SNV), the clinical and biological significance of these mutations remains uncharacterized. Through targeted re-sequencing, we identified mutations of MLL2 in 8 % (14/175) of MBs, the majority of which were loss of function. Notably, we also report mutations affecting the MLL2-binding partner KDM6A, in 4 % (7/175) of tumors. While MLL2 mutations were independent of age, gender, histological subtype, M-stage or molecular subgroup, KDM6A mutations were most commonly identified in Group 4 MBs, and were mutually exclusive with MLL2 mutations. Immunohistochemical staining for H3K4me3 and H3K27me3, the chromatin effectors of MLL2 and KDM6A activity, respectively, demonstrated alterations of the histone code in 24 % (53/220) of MBs across all subgroups. Correlating these MLL2- and KDM6A-driven histone marks with prognosis, we identified populations of MB with improved (K4+/K27-) and dismal (K4-/K27-) outcomes, observed primarily within Group 3 and 4 MBs. Group 3 and 4 MBs demonstrate somatic copy number aberrations, and transcriptional profiles that converge on modifiers of H3K27-methylation (EZH2, KDM6A, KDM6B), leading to silencing of PRC2-target genes. As PRC2-mediated aberrant methylation of H3K27 has recently been targeted for therapy in other diseases, it represents an actionable target for a substantial percentage of medulloblastoma patients with aggressive forms of the disease. More... »
PAGES373-384
http://scigraph.springernature.com/pub.10.1007/s00401-012-1070-9
DOIhttp://dx.doi.org/10.1007/s00401-012-1070-9
DIMENSIONShttps://app.dimensions.ai/details/publication/pub.1050474011
PUBMEDhttps://www.ncbi.nlm.nih.gov/pubmed/23184418
JSON-LD is the canonical representation for SciGraph data.
TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT
[
{
"@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json",
"about": [
{
"id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/0604",
"inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/",
"name": "Genetics",
"type": "DefinedTerm"
},
{
"id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/06",
"inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/",
"name": "Biological Sciences",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Base Sequence",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Cerebellar Neoplasms",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Cohort Studies",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "DNA-Binding Proteins",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Female",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Genetic Predisposition to Disease",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Genome",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Histone Demethylases",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Histone-Lysine N-Methyltransferase",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Humans",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Lysine",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Male",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Medulloblastoma",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Methylation",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Mutation",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Neoplasm Proteins",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Nuclear Proteins",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Polymorphism, Single Nucleotide",
"type": "DefinedTerm"
}
],
"author": [
{
"affiliation": {
"alternateName": "University of Toronto",
"id": "https://www.grid.ac/institutes/grid.17063.33",
"name": [
"Division of Neurosurgery, Arthur & Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada",
"Program in Developmental & Stem Cell Biology, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada",
"Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada"
],
"type": "Organization"
},
"familyName": "Dubuc",
"givenName": "Adrian M.",
"id": "sg:person.0730625032.39",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0730625032.39"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "University of Toronto",
"id": "https://www.grid.ac/institutes/grid.17063.33",
"name": [
"Division of Neurosurgery, Arthur & Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada",
"Program in Developmental & Stem Cell Biology, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada",
"Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada"
],
"type": "Organization"
},
"familyName": "Remke",
"givenName": "Marc",
"id": "sg:person.01001656432.42",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01001656432.42"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "German Cancer Research Center",
"id": "https://www.grid.ac/institutes/grid.7497.d",
"name": [
"CCU Neuropathology, German Cancer Research Centre (DKFZ), Heidelberg, Germany",
"Department of Neuropathology, University of Heidelberg, Heidelberg, Germany",
"Division of Pediatric Neurooncology, German Cancer Research Centre (DKFZ), Heidelberg, Germany"
],
"type": "Organization"
},
"familyName": "Korshunov",
"givenName": "Andrey",
"id": "sg:person.013472071457.40",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013472071457.40"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "German Cancer Research Center",
"id": "https://www.grid.ac/institutes/grid.7497.d",
"name": [
"Division of Pediatric Neurooncology, German Cancer Research Centre (DKFZ), Heidelberg, Germany"
],
"type": "Organization"
},
"familyName": "Northcott",
"givenName": "Paul A.",
"id": "sg:person.010563327577.08",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010563327577.08"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "BC Cancer Agency",
"id": "https://www.grid.ac/institutes/grid.248762.d",
"name": [
"Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC, Canada"
],
"type": "Organization"
},
"familyName": "Zhan",
"givenName": "Shing H.",
"id": "sg:person.0722075723.46",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0722075723.46"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "BC Cancer Agency",
"id": "https://www.grid.ac/institutes/grid.248762.d",
"name": [
"Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC, Canada"
],
"type": "Organization"
},
"familyName": "Mendez-Lago",
"givenName": "Maria",
"id": "sg:person.01247107342.55",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01247107342.55"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "German Cancer Research Center",
"id": "https://www.grid.ac/institutes/grid.7497.d",
"name": [
"Division of Pediatric Neurooncology, German Cancer Research Centre (DKFZ), Heidelberg, Germany"
],
"type": "Organization"
},
"familyName": "Kool",
"givenName": "Marcel",
"type": "Person"
},
{
"affiliation": {
"alternateName": "German Cancer Research Center",
"id": "https://www.grid.ac/institutes/grid.7497.d",
"name": [
"Division of Pediatric Neurooncology, German Cancer Research Centre (DKFZ), Heidelberg, Germany"
],
"type": "Organization"
},
"familyName": "Jones",
"givenName": "David T. W.",
"id": "sg:person.011536141544.42",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.011536141544.42"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Hospital for Sick Children",
"id": "https://www.grid.ac/institutes/grid.42327.30",
"name": [
"Division of Neurosurgery, Arthur & Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada",
"Program in Developmental & Stem Cell Biology, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada"
],
"type": "Organization"
},
"familyName": "Unterberger",
"givenName": "Alexander",
"id": "sg:person.01214325117.82",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01214325117.82"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Hospital for Sick Children",
"id": "https://www.grid.ac/institutes/grid.42327.30",
"name": [
"Division of Neurosurgery, Arthur & Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada",
"Program in Developmental & Stem Cell Biology, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada"
],
"type": "Organization"
},
"familyName": "Morrissy",
"givenName": "A. Sorana",
"id": "sg:person.01040422763.65",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01040422763.65"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "University of Toronto",
"id": "https://www.grid.ac/institutes/grid.17063.33",
"name": [
"Division of Neurosurgery, Arthur & Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada",
"Program in Developmental & Stem Cell Biology, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada",
"Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada"
],
"type": "Organization"
},
"familyName": "Shih",
"givenName": "David",
"id": "sg:person.014330027137.35",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014330027137.35"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "University of Toronto",
"id": "https://www.grid.ac/institutes/grid.17063.33",
"name": [
"Division of Neurosurgery, Arthur & Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada",
"Program in Developmental & Stem Cell Biology, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada",
"Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada"
],
"type": "Organization"
},
"familyName": "Peacock",
"givenName": "John",
"type": "Person"
},
{
"affiliation": {
"alternateName": "University of Toronto",
"id": "https://www.grid.ac/institutes/grid.17063.33",
"name": [
"Division of Neurosurgery, Arthur & Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada",
"Program in Developmental & Stem Cell Biology, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada",
"Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada"
],
"type": "Organization"
},
"familyName": "Ramaswamy",
"givenName": "Vijay",
"id": "sg:person.0662511632.27",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0662511632.27"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Hospital for Sick Children",
"id": "https://www.grid.ac/institutes/grid.42327.30",
"name": [
"Division of Neurosurgery, Arthur & Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada",
"Program in Developmental & Stem Cell Biology, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada"
],
"type": "Organization"
},
"familyName": "Rolider",
"givenName": "Adi",
"id": "sg:person.014364622424.83",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014364622424.83"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "University of Toronto",
"id": "https://www.grid.ac/institutes/grid.17063.33",
"name": [
"Division of Neurosurgery, Arthur & Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada",
"Program in Developmental & Stem Cell Biology, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada",
"Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada"
],
"type": "Organization"
},
"familyName": "Wang",
"givenName": "Xin",
"id": "sg:person.0722072325.07",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0722072325.07"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "German Cancer Research Center",
"id": "https://www.grid.ac/institutes/grid.7497.d",
"name": [
"Division of Pediatric Neurooncology, German Cancer Research Centre (DKFZ), Heidelberg, Germany"
],
"type": "Organization"
},
"familyName": "Witt",
"givenName": "Hendrik",
"id": "sg:person.0757363774.37",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0757363774.37"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "German Cancer Research Center",
"id": "https://www.grid.ac/institutes/grid.7497.d",
"name": [
"Division of Pediatric Neurooncology, German Cancer Research Centre (DKFZ), Heidelberg, Germany"
],
"type": "Organization"
},
"familyName": "Hielscher",
"givenName": "Thomas",
"id": "sg:person.0751543667.09",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0751543667.09"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "University of Toronto",
"id": "https://www.grid.ac/institutes/grid.17063.33",
"name": [
"Division of Neurosurgery, Arthur & Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada",
"Program in Developmental & Stem Cell Biology, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada",
"Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada"
],
"type": "Organization"
},
"familyName": "Hawkins",
"givenName": "Cynthia",
"type": "Person"
},
{
"affiliation": {
"alternateName": "University of Colorado Anschutz Medical Campus",
"id": "https://www.grid.ac/institutes/grid.430503.1",
"name": [
"Department of Pediatrics, The Children\u2019s Hospital and University of Colorado, Anschutz Medical Campus, Colorado, USA"
],
"type": "Organization"
},
"familyName": "Vibhakar",
"givenName": "Rajeev",
"id": "sg:person.0604547446.53",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0604547446.53"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "University of Toronto",
"id": "https://www.grid.ac/institutes/grid.17063.33",
"name": [
"Department of Pathology, University Health Network, University of Toronto, Toronto, ON, Canada"
],
"type": "Organization"
},
"familyName": "Croul",
"givenName": "Sidney",
"type": "Person"
},
{
"affiliation": {
"alternateName": "University of Toronto",
"id": "https://www.grid.ac/institutes/grid.17063.33",
"name": [
"Division of Neurosurgery, Arthur & Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada",
"Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada"
],
"type": "Organization"
},
"familyName": "Rutka",
"givenName": "James T.",
"id": "sg:person.0731527271.09",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0731527271.09"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "University of California, San Francisco",
"id": "https://www.grid.ac/institutes/grid.266102.1",
"name": [
"Helen Diller Family Comprehensive Cancer Centre, University of California, San Francisco, CA, USA"
],
"type": "Organization"
},
"familyName": "Weiss",
"givenName": "William A.",
"id": "sg:person.01362073334.54",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01362073334.54"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "BC Cancer Agency",
"id": "https://www.grid.ac/institutes/grid.248762.d",
"name": [
"Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC, Canada"
],
"type": "Organization"
},
"familyName": "Jones",
"givenName": "Steven J. M.",
"id": "sg:person.011076371162.80",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.011076371162.80"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Johns Hopkins University",
"id": "https://www.grid.ac/institutes/grid.21107.35",
"name": [
"Department of Pathology, Johns Hopkins University, Baltimore, MD, USA"
],
"type": "Organization"
},
"familyName": "Eberhart",
"givenName": "Charles G.",
"id": "sg:person.0775321062.58",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0775321062.58"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "BC Cancer Agency",
"id": "https://www.grid.ac/institutes/grid.248762.d",
"name": [
"Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC, Canada"
],
"type": "Organization"
},
"familyName": "Marra",
"givenName": "Marco A.",
"id": "sg:person.01150455763.02",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01150455763.02"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "German Cancer Research Center",
"id": "https://www.grid.ac/institutes/grid.7497.d",
"name": [
"Division of Pediatric Neurooncology, German Cancer Research Centre (DKFZ), Heidelberg, Germany"
],
"type": "Organization"
},
"familyName": "Pfister",
"givenName": "Stefan M.",
"id": "sg:person.01105171247.76",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01105171247.76"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "University of Toronto",
"id": "https://www.grid.ac/institutes/grid.17063.33",
"name": [
"Division of Neurosurgery, Arthur & Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada",
"Program in Developmental & Stem Cell Biology, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada",
"Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada"
],
"type": "Organization"
},
"familyName": "Taylor",
"givenName": "Michael D.",
"id": "sg:person.012731463207.92",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012731463207.92"
],
"type": "Person"
}
],
"citation": [
{
"id": "sg:pub.10.1038/nature11606",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1000463489",
"https://doi.org/10.1038/nature11606"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1200/jco.2005.01.5479",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1001500983"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/ng.349",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1001520036",
"https://doi.org/10.1038/ng.349"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1007/s00401-012-0958-8",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1007662906",
"https://doi.org/10.1007/s00401-012-0958-8"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.3747/co.v16i6.435",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1008321803"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1007/s00401-011-0922-z",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1012707701",
"https://doi.org/10.1007/s00401-011-0922-z"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1200/jco.2010.31.1670",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1014934168"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1158/1078-0432.ccr-08-2786",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1016232380"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/nature10351",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1019649945",
"https://doi.org/10.1038/nature10351"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1242/dev.02302",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1025723258"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1242/dev.02302",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1025723258"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1200/jco.2009.27.4324",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1026297279"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1371/journal.pbio.1000453",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1028812864"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1371/journal.pbio.1000453",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1028812864"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1126/science.1198056",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1030704690"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1016/j.cell.2007.02.009",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1032874898"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1200/jco.2010.28.1675",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1032904399"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1158/0008-5472.can-08-0946",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1033825742"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/ng.336",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1035880217",
"https://doi.org/10.1038/ng.336"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/nature11329",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1036872856",
"https://doi.org/10.1038/nature11329"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/nrm3230",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1039186368",
"https://doi.org/10.1038/nrm3230"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/nature11284",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1039302414",
"https://doi.org/10.1038/nature11284"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/nature11213",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1040240428",
"https://doi.org/10.1038/nature11213"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1093/bioinformatics/btr100",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1042699958"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1002/ijc.27455",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1046972454"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1056/nejmoa0902903",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1048045488"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1371/journal.pone.0003088",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1049915735"
],
"type": "CreativeWork"
}
],
"datePublished": "2013-03",
"datePublishedReg": "2013-03-01",
"description": "Recent sequencing efforts have described the mutational landscape of the pediatric brain tumor medulloblastoma. Although MLL2 is among the most frequent somatic single nucleotide variants (SNV), the clinical and biological significance of these mutations remains uncharacterized. Through targeted re-sequencing, we identified mutations of MLL2 in 8 % (14/175) of MBs, the majority of which were loss of function. Notably, we also report mutations affecting the MLL2-binding partner KDM6A, in 4 % (7/175) of tumors. While MLL2 mutations were independent of age, gender, histological subtype, M-stage or molecular subgroup, KDM6A mutations were most commonly identified in Group 4 MBs, and were mutually exclusive with MLL2 mutations. Immunohistochemical staining for H3K4me3 and H3K27me3, the chromatin effectors of MLL2 and KDM6A activity, respectively, demonstrated alterations of the histone code in 24 % (53/220) of MBs across all subgroups. Correlating these MLL2- and KDM6A-driven histone marks with prognosis, we identified populations of MB with improved (K4+/K27-) and dismal (K4-/K27-) outcomes, observed primarily within Group 3 and 4 MBs. Group 3 and 4 MBs demonstrate somatic copy number aberrations, and transcriptional profiles that converge on modifiers of H3K27-methylation (EZH2, KDM6A, KDM6B), leading to silencing of PRC2-target genes. As PRC2-mediated aberrant methylation of H3K27 has recently been targeted for therapy in other diseases, it represents an actionable target for a substantial percentage of medulloblastoma patients with aggressive forms of the disease.",
"genre": "research_article",
"id": "sg:pub.10.1007/s00401-012-1070-9",
"inLanguage": [
"en"
],
"isAccessibleForFree": true,
"isFundedItemOf": [
{
"id": "sg:grant.2480799",
"type": "MonetaryGrant"
},
{
"id": "sg:grant.2415500",
"type": "MonetaryGrant"
},
{
"id": "sg:grant.2481457",
"type": "MonetaryGrant"
},
{
"id": "sg:grant.2438855",
"type": "MonetaryGrant"
}
],
"isPartOf": [
{
"id": "sg:journal.1019073",
"issn": [
"0001-6322",
"1432-0533"
],
"name": "Acta Neuropathologica",
"type": "Periodical"
},
{
"issueNumber": "3",
"type": "PublicationIssue"
},
{
"type": "PublicationVolume",
"volumeNumber": "125"
}
],
"name": "Aberrant patterns of H3K4 and H3K27 histone lysine methylation occur across subgroups in medulloblastoma",
"pagination": "373-384",
"productId": [
{
"name": "readcube_id",
"type": "PropertyValue",
"value": [
"f070f98c714a933ad033cc7235bba4e0b7f90b24fbed6b3feb717009aa75aae1"
]
},
{
"name": "pubmed_id",
"type": "PropertyValue",
"value": [
"23184418"
]
},
{
"name": "nlm_unique_id",
"type": "PropertyValue",
"value": [
"0412041"
]
},
{
"name": "doi",
"type": "PropertyValue",
"value": [
"10.1007/s00401-012-1070-9"
]
},
{
"name": "dimensions_id",
"type": "PropertyValue",
"value": [
"pub.1050474011"
]
}
],
"sameAs": [
"https://doi.org/10.1007/s00401-012-1070-9",
"https://app.dimensions.ai/details/publication/pub.1050474011"
],
"sdDataset": "articles",
"sdDatePublished": "2019-04-10T18:16",
"sdLicense": "https://scigraph.springernature.com/explorer/license/",
"sdPublisher": {
"name": "Springer Nature - SN SciGraph project",
"type": "Organization"
},
"sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000001_0000000264/records_8675_00000491.jsonl",
"type": "ScholarlyArticle",
"url": "http://link.springer.com/10.1007/s00401-012-1070-9"
}
]Download the RDF metadata as:Â json-ld nt turtle xml License info
JSON-LD is a popular format for linked data which is fully compatible with JSON.
curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1007/s00401-012-1070-9'
N-Triples is a line-based linked data format ideal for batch operations.
curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1007/s00401-012-1070-9'
Turtle is a human-readable linked data format.
curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1007/s00401-012-1070-9'
RDF/XML is a standard XML format for linked data.
curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1007/s00401-012-1070-9'
This table displays all metadata directly associated to this object as RDF triples.
436 TRIPLES
21 PREDICATES
72 URIs
39 LITERALS
27 BLANK NODES