Linked Life Data

17647283

Source:http://linkedlifedata.com/resource/pubmed/id/17647283

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2007-8-7
pubmed:abstractText
Neuroblastoma is a heterogeneous neoplasm that has served as a paradigm for the clinical utility of somatically acquired genomic aberrations. DNA copy number alterations (CNA) are currently used to predict prognosis, including MYCN amplification and deletions at chromosome bands 1p36 and 11q23. We predicted that genome-wide assessment of DNA aberrations in neuroblastoma tumors would provide a more precise estimation of clinical phenotype, and could be used to predict outcome. We measured CNAs in a representative set of 82 diagnostic tumors on a customized high-resolution BAC array-based CGH platform supplemented with additional clones across 1p36, 2p24, 3p21-22, 11q14-24, and 16p12-13, and integrated these data with RNA expression data. We used an unbiased statistical method to define a set of minimal common regions (MCRs) of aberration. Unsupervised hierarchical clustering identified four distinct genomic subclasses. First, a subset of tumors with a clinically benign phenotype showed predominantly whole chromosome gains and losses. Second, tumors with MYCN amplification had a unique genomic signature of 1p deletion and 17q gain, but few other rearrangements. Third, tumors with an aggressive clinical phenotype without MYCN amplification, showed multiple structural rearrangements. Most notable were deletions of 3p, 4p, and 11q and gain of 1q, 2p, 12q, and 17q. Lastly, there was a subset of tumors with an aggressive clinical phenotype and no detectable DNA CNAs. The genomic subsets were highly correlated with patient outcome, and individual MCRs remained prognostic in a multivariable model. DNA signature patterns embed important prognostic information in diagnostic neuroblastoma samples, and can identify candidate cancer-related genes.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1045-2257
pubmed:author
pubmed:copyrightInfo
Copyright (c) 2007 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:volume
46
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
936-49
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:17647283-Chromosomes, Human, Pair 11, pubmed-meshheading:17647283-DNA, Neoplasm, pubmed-meshheading:17647283-DNA Methylation, pubmed-meshheading:17647283-DNA-Binding Proteins, pubmed-meshheading:17647283-Gene Dosage, pubmed-meshheading:17647283-Gene Expression Regulation, Neoplastic, pubmed-meshheading:17647283-Humans, pubmed-meshheading:17647283-In Situ Hybridization, Fluorescence, pubmed-meshheading:17647283-Infant, pubmed-meshheading:17647283-Insulin-Like Growth Factor II, pubmed-meshheading:17647283-Loss of Heterozygosity, pubmed-meshheading:17647283-Neuroblastoma, pubmed-meshheading:17647283-Nucleic Acid Hybridization, pubmed-meshheading:17647283-Oncogene Proteins, Fusion, pubmed-meshheading:17647283-Phenotype, pubmed-meshheading:17647283-Prognosis, pubmed-meshheading:17647283-Proteins, pubmed-meshheading:17647283-Repressor Proteins, pubmed-meshheading:17647283-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:17647283-Survival Rate
pubmed:year
2007
pubmed:articleTitle
Neuroblastomas have distinct genomic DNA profiles that predict clinical phenotype and regional gene expression.
pubmed:affiliation
Division of Oncology, Children's Hospital of Philadelphia, and Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. mosse@email.chop.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural