Ontology type: schema:ScholarlyArticle Open Access: True
2000-10-01
AUTHORSAndrea R Florl, Knut H Franke, Dieter Niederacher, Claus-Dieter Gerharz, Hans-Helge Seifert, Wolfgang A Schulz
ABSTRACTAlterations of the CDKN2A locus on chromosome 9p21 encoding the p16INK4A cell cycle regulator and the p14ARF1 p53 activator proteins are frequently found in bladder cancer. Here, we present an analysis of 86 transitional cell carcinomas (TCC) to elucidate the mechanisms responsible for inactivation of this locus. Multiplex quantitative PCR analysis for five microsatellites around the locus showed that 34 tumors (39%) had loss of heterozygosity (LOH) generally encompassing the entire region. Of these, 17 tumors (20%) carried homozygous deletions of at least one CDKN2A exon and of flanking microsatellites, as detected by quantitative PCR. Analysis by restriction enzyme PCR and methylation-specific PCR showed that only three specimens, each with LOH across 9p21, had bona fide hypermethylation of the CDKN2A exon 1α CpG-island in the remaining allele. Like most other specimens, these three specimens displayed substantial genome-wide hypomethylation of DNA as reflected in the methylation status of LINE L1 sequences. The extent of DNA hypomethylation was significantly more pronounced in TCC with LOH and/or homozygous deletions at 9p21 than in those without (26% and 28%, respectively, on average, versus 11%, p < 0.0015). No association of LOH or homozygous deletions at 9p21 with tumor stage or grade was found. The data indicate that DNA hypermethylation may be rare in TCC and that deletions are the most important mechanism for inactivation of the CDKN2A locus. The predominance of allelic loss may be explained by its correlation with genome-wide DNA hypomethylation, which is thought to favor chromosomal instability and illegitimate recombination. More... »
PAGES1513-1522
http://scigraph.springernature.com/pub.10.1038/labinvest.3780161
DOIhttp://dx.doi.org/10.1038/labinvest.3780161
DIMENSIONShttps://app.dimensions.ai/details/publication/pub.1013600487
PUBMEDhttps://www.ncbi.nlm.nih.gov/pubmed/11045568
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/2008/11",
"inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/",
"name": "Medical and Health Sciences",
"type": "DefinedTerm"
},
{
"id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1103",
"inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/",
"name": "Clinical Sciences",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Adult",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Aged",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Aged, 80 and over",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Carcinoma, Transitional Cell",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Chromosome Mapping",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Cyclin-Dependent Kinase Inhibitor p16",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "DNA Methylation",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Female",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Humans",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Loss of Heterozygosity",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Male",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Middle Aged",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Tumor Cells, Cultured",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Urinary Bladder Neoplasms",
"type": "DefinedTerm"
}
],
"author": [
{
"affiliation": {
"alternateName": "Urologische Klinik, Heinrich Heine Universit\u00e4t, D\u00fcsseldorf, Germany",
"id": "http://www.grid.ac/institutes/grid.411327.2",
"name": [
"Urologische Klinik, Heinrich Heine Universit\u00e4t, D\u00fcsseldorf, Germany"
],
"type": "Organization"
},
"familyName": "Florl",
"givenName": "Andrea R",
"id": "sg:person.0633563070.03",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0633563070.03"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Urologische Klinik, Heinrich Heine Universit\u00e4t, D\u00fcsseldorf, Germany",
"id": "http://www.grid.ac/institutes/grid.411327.2",
"name": [
"Urologische Klinik, Heinrich Heine Universit\u00e4t, D\u00fcsseldorf, Germany"
],
"type": "Organization"
},
"familyName": "Franke",
"givenName": "Knut H",
"id": "sg:person.0666535067.23",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0666535067.23"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Frauenklinik, Heinrich Heine Universit\u00e4t, D\u00fcsseldorf, Germany",
"id": "http://www.grid.ac/institutes/grid.411327.2",
"name": [
"Frauenklinik, Heinrich Heine Universit\u00e4t, D\u00fcsseldorf, Germany"
],
"type": "Organization"
},
"familyName": "Niederacher",
"givenName": "Dieter",
"id": "sg:person.01045060062.80",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01045060062.80"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Institut f\u00fcr Pathologie, Heinrich Heine Universit\u00e4t, D\u00fcsseldorf, Germany",
"id": "http://www.grid.ac/institutes/grid.411327.2",
"name": [
"Institut f\u00fcr Pathologie, Heinrich Heine Universit\u00e4t, D\u00fcsseldorf, Germany"
],
"type": "Organization"
},
"familyName": "Gerharz",
"givenName": "Claus-Dieter",
"id": "sg:person.0702447147.68",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0702447147.68"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Urologische Klinik, Heinrich Heine Universit\u00e4t, D\u00fcsseldorf, Germany",
"id": "http://www.grid.ac/institutes/grid.411327.2",
"name": [
"Urologische Klinik, Heinrich Heine Universit\u00e4t, D\u00fcsseldorf, Germany"
],
"type": "Organization"
},
"familyName": "Seifert",
"givenName": "Hans-Helge",
"id": "sg:person.01257674641.78",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01257674641.78"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Urologische Klinik, Heinrich Heine Universit\u00e4t, D\u00fcsseldorf, Germany",
"id": "http://www.grid.ac/institutes/grid.411327.2",
"name": [
"Urologische Klinik, Heinrich Heine Universit\u00e4t, D\u00fcsseldorf, Germany"
],
"type": "Organization"
},
"familyName": "Schulz",
"givenName": "Wolfgang A",
"id": "sg:person.01270311431.19",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01270311431.19"
],
"type": "Person"
}
],
"citation": [
{
"id": "sg:pub.10.1038/25779",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1049909374",
"https://doi.org/10.1038/25779"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/ng0598-19",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1033511786",
"https://doi.org/10.1038/ng0598-19"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/46052",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1052544917",
"https://doi.org/10.1038/46052"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1007/s002400050050",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1040677037",
"https://doi.org/10.1007/s002400050050"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/sj.bjc.6690524",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1025154261",
"https://doi.org/10.1038/sj.bjc.6690524"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/nm0795-686",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1016345098",
"https://doi.org/10.1038/nm0795-686"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/sj.onc.1202385",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1024660747",
"https://doi.org/10.1038/sj.onc.1202385"
],
"type": "CreativeWork"
}
],
"datePublished": "2000-10-01",
"datePublishedReg": "2000-10-01",
"description": "Alterations of the CDKN2A locus on chromosome 9p21 encoding the p16INK4A cell cycle regulator and the p14ARF1 p53 activator proteins are frequently found in bladder cancer. Here, we present an analysis of 86 transitional cell carcinomas (TCC) to elucidate the mechanisms responsible for inactivation of this locus. Multiplex quantitative PCR analysis for five microsatellites around the locus showed that 34 tumors (39%) had loss of heterozygosity (LOH) generally encompassing the entire region. Of these, 17 tumors (20%) carried homozygous deletions of at least one CDKN2A exon and of flanking microsatellites, as detected by quantitative PCR. Analysis by restriction enzyme PCR and methylation-specific PCR showed that only three specimens, each with LOH across 9p21, had bona fide hypermethylation of the CDKN2A exon 1\u03b1 CpG-island in the remaining allele. Like most other specimens, these three specimens displayed substantial genome-wide hypomethylation of DNA as reflected in the methylation status of LINE L1 sequences. The extent of DNA hypomethylation was significantly more pronounced in TCC with LOH and/or homozygous deletions at 9p21 than in those without (26% and 28%, respectively, on average, versus 11%, p < 0.0015). No association of LOH or homozygous deletions at 9p21 with tumor stage or grade was found. The data indicate that DNA hypermethylation may be rare in TCC and that deletions are the most important mechanism for inactivation of the CDKN2A locus. The predominance of allelic loss may be explained by its correlation with genome-wide DNA hypomethylation, which is thought to favor chromosomal instability and illegitimate recombination.",
"genre": "article",
"id": "sg:pub.10.1038/labinvest.3780161",
"isAccessibleForFree": true,
"isPartOf": [
{
"id": "sg:journal.1017964",
"issn": [
"0023-6837",
"1530-0307"
],
"name": "Laboratory Investigation",
"publisher": "Springer Nature",
"type": "Periodical"
},
{
"issueNumber": "10",
"type": "PublicationIssue"
},
{
"type": "PublicationVolume",
"volumeNumber": "80"
}
],
"keywords": [
"loss of heterozygosity",
"DNA hypomethylation",
"genome-wide DNA hypomethylation",
"CDKN2A locus",
"genome-wide hypomethylation",
"homozygous deletion",
"cell cycle regulators",
"quantitative PCR analysis",
"activator protein",
"illegitimate recombination",
"DNA methylation",
"CpG islands",
"methylation-specific PCR",
"DNA hypermethylation",
"cycle regulators",
"chromosomal instability",
"methylation status",
"L1 sequences",
"loci",
"PCR analysis",
"hypomethylation",
"chromosome 9p21",
"deletion",
"quantitative PCR",
"microsatellites",
"association of LOH",
"CDKN2A inactivation",
"hypermethylation",
"important mechanism",
"inactivation",
"allelic loss",
"PCR",
"exons",
"methylation",
"heterozygosity",
"regulator",
"mechanism",
"protein",
"DNA",
"alleles",
"recombination",
"sequence",
"entire region",
"cell carcinoma",
"alterations",
"loss",
"specimens",
"analysis",
"region",
"stage",
"cancer",
"tumors",
"bladder cancer",
"tumor stage",
"association",
"predominance",
"extent",
"carcinoma",
"status",
"data",
"transitional cell carcinoma",
"instability",
"correlation",
"urinary bladder",
"bladder",
"grade"
],
"name": "DNA Methylation and the Mechanisms of CDKN2A Inactivation in Transitional Cell Carcinoma of the Urinary Bladder",
"pagination": "1513-1522",
"productId": [
{
"name": "dimensions_id",
"type": "PropertyValue",
"value": [
"pub.1013600487"
]
},
{
"name": "doi",
"type": "PropertyValue",
"value": [
"10.1038/labinvest.3780161"
]
},
{
"name": "pubmed_id",
"type": "PropertyValue",
"value": [
"11045568"
]
}
],
"sameAs": [
"https://doi.org/10.1038/labinvest.3780161",
"https://app.dimensions.ai/details/publication/pub.1013600487"
],
"sdDataset": "articles",
"sdDatePublished": "2022-08-04T16:54",
"sdLicense": "https://scigraph.springernature.com/explorer/license/",
"sdPublisher": {
"name": "Springer Nature - SN SciGraph project",
"type": "Organization"
},
"sdSource": "s3://com-springernature-scigraph/baseset/20220804/entities/gbq_results/article/article_318.jsonl",
"type": "ScholarlyArticle",
"url": "https://doi.org/10.1038/labinvest.3780161"
}
]Download the RDF metadata as: 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.10.1038/labinvest.3780161'
N-Triples is a line-based linked data format ideal for batch operations.
curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/labinvest.3780161'
Turtle is a human-readable linked data format.
curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/labinvest.3780161'
RDF/XML is a standard XML format for linked data.
curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/labinvest.3780161'
This table displays all metadata directly associated to this object as RDF triples.
250 TRIPLES
21 PREDICATES
112 URIs
97 LITERALS
21 BLANK NODES