Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
23
pubmed:dateCreated
2006-12-5
pubmed:abstractText
Most Wilms' tumors are of low stage, favorable histology, and have a high likelihood of cure with current multimodal therapy. Despite this, there remains a group of patients whose tumors recur for whom intensive salvage regimens result in survival of only 50%. Fitting a Cox proportional hazards model to microarray-based comparative genomic hybridization (aCGH) data on 68 Wilms' tumor samples, we identified a significant correlation between increased copy number at chromosome 15q26.3 insulin-like growth factor I receptor (IGFIR) and tumor relapse (adjusted P = 0.014). Wilms' tumors (13%) exhibited a low-level gain corresponding to three to four copies of the gene by aCGH analysis, 9 of 10 of which exhibited high IGFIR mRNA levels. Although IGFIR protein expression was restricted to the epithelial cells of fetal kidney and Wilms' tumors in most cases, 12% of tumors were also found to express IGFIR in the blastemal compartment. Blastemal IGFIR protein expression was associated with an increased copy number and a shorter relapse-free survival time (P = 0.027, log-rank test). In addition to the membrane localization, IGFIR was localized to the perinuclear region of the blastemal cells in 6% of Wilms' tumors. These data provide evidence that an increase in IGFIR gene copy number results in aberrant expression in the blastemal compartment of some Wilms' tumors and is associated with an adverse outcome in these patients. These findings suggest the possibility of use of targeted agents in the therapy of these children.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
66
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
11148-55
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:17145858-Cell Nucleus, pubmed-meshheading:17145858-Chromosomes, Human, Pair 15, pubmed-meshheading:17145858-Epithelial Cells, pubmed-meshheading:17145858-Gene Dosage, pubmed-meshheading:17145858-Gene Expression Regulation, Neoplastic, pubmed-meshheading:17145858-Genome, Human, pubmed-meshheading:17145858-Humans, pubmed-meshheading:17145858-Immunohistochemistry, pubmed-meshheading:17145858-In Situ Hybridization, Fluorescence, pubmed-meshheading:17145858-Kaplan-Meier Estimate, pubmed-meshheading:17145858-Kidney, pubmed-meshheading:17145858-Kidney Neoplasms, pubmed-meshheading:17145858-Neoplasm Recurrence, Local, pubmed-meshheading:17145858-Nucleic Acid Hybridization, pubmed-meshheading:17145858-Prognosis, pubmed-meshheading:17145858-Proportional Hazards Models, pubmed-meshheading:17145858-Receptor, IGF Type 1, pubmed-meshheading:17145858-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:17145858-Wilms Tumor
pubmed:year
2006
pubmed:articleTitle
Blastemal expression of type I insulin-like growth factor receptor in Wilms' tumors is driven by increased copy number and correlates with relapse.
pubmed:affiliation
Paediatric Oncology, Institute of Cancer Research/Royal Marsden National Health Service Trust, Sutton, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't