Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1993-4-20
pubmed:abstractText
Reduced expression of nm23 RNAs/proteins has been associated previously with high tumor metastatic potential. In contrast, we report that regional (state III) and metastatic (stage IV) childhood neuroblastomas exhibit elevated nm23 RNA levels as compared with localized tumors. Elevated neuroblastoma nm23 RNA levels were associated with significant reductions in patient survival in the overall (n = 75) and N-myc non-amplified (n = 61) portion of the cohort. Amplification of the chromosomal nm23-H1 gene was observed in 6/18 stage III and IV tumors; amplification of nm23-H2 was not demonstrated. Genomic amplification of nm23-H1 was associated with increased tumor nm23 RNA expression and reduced patient survival. Single-strand conformational polymorphism (SSCP) analysis was performed on seven neuroblastomas. Minor subpopulations of cDNAs exhibiting altered mobility were apparent in both nm23-H1 and nm23-H2 translated regions of stage III and IV tumors, suggestive of mutations. Confirmation of the SSCP data was provided by direct sequencing of nm23-H2 in a stage IV tumor, revealing a leucine to valine mutation at position 48. The data indicate that molecular alterations to nm23 other than its reduced expression can be associated with tumor aggressiveness, and provide the first evidence for nm23 mutation in a human cancer.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
855-65
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:8384356-Amino Acid Sequence, pubmed-meshheading:8384356-Base Sequence, pubmed-meshheading:8384356-Child, pubmed-meshheading:8384356-Child, Preschool, pubmed-meshheading:8384356-DNA, Neoplasm, pubmed-meshheading:8384356-Gene Amplification, pubmed-meshheading:8384356-Gene Expression Regulation, Neoplastic, pubmed-meshheading:8384356-Genes, myc, pubmed-meshheading:8384356-Humans, pubmed-meshheading:8384356-Infant, pubmed-meshheading:8384356-Molecular Sequence Data, pubmed-meshheading:8384356-Monomeric GTP-Binding Proteins, pubmed-meshheading:8384356-Mutation, pubmed-meshheading:8384356-NM23 Nucleoside Diphosphate Kinases, pubmed-meshheading:8384356-Neoplasm Staging, pubmed-meshheading:8384356-Neuroblastoma, pubmed-meshheading:8384356-Nucleoside-Diphosphate Kinase, pubmed-meshheading:8384356-Oligodeoxyribonucleotides, pubmed-meshheading:8384356-Polymerase Chain Reaction, pubmed-meshheading:8384356-Prognosis, pubmed-meshheading:8384356-Proteins, pubmed-meshheading:8384356-RNA, Messenger, pubmed-meshheading:8384356-RNA, Neoplasm, pubmed-meshheading:8384356-Survival Analysis, pubmed-meshheading:8384356-Transcription Factors
pubmed:year
1993
pubmed:articleTitle
Evidence for nm23 RNA overexpression, DNA amplification and mutation in aggressive childhood neuroblastomas.
pubmed:affiliation
Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't