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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2001-8-24
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pubmed:abstractText |
Activating point mutations in codons 12, 13, or 61 of the K-ras and N-ras genes have been reported to occur in up to 40% of patients with multiple myeloma at presentation. In a study of 34 presentation myeloma cases using a sensitive polymerase chain reaction-restriction fragment length polymorphism strategy on enriched tumor cell populations, the present study detected N-ras codon 61 mutation-positive cells in all patients. Quantitative plaque hybridization using allele-specific oligonucleotide probes showed that in the majority of patients, ras mutation-positive cells comprise only a subpopulation of the total malignant plasma cell compartment (range, 12%-100%). Using clonospecific point mutations in the 5' untranslated region of the BCL6 gene to quantitate clonal B cells in FACS-sorted bone marrow populations from 2 patients, the representation of ras mutation-positive cells was independent of immunophenotype. These observations imply that mutational activation of N-ras codon 61 is a mandatory event in the pathogenesis of multiple myeloma; such mutations provide a marker of intraclonal heterogeneity that may originate at an earlier ontologic stage than immunophenotypic diversification of the malignant B cell clone.
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0006-4971
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
98
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1555-60
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:11520807-5' Untranslated Regions,
pubmed-meshheading:11520807-Amino Acid Substitution,
pubmed-meshheading:11520807-Cell Separation,
pubmed-meshheading:11520807-Cell Transformation, Neoplastic,
pubmed-meshheading:11520807-Clone Cells,
pubmed-meshheading:11520807-Codon,
pubmed-meshheading:11520807-DNA, Neoplasm,
pubmed-meshheading:11520807-DNA Mutational Analysis,
pubmed-meshheading:11520807-DNA-Binding Proteins,
pubmed-meshheading:11520807-Female,
pubmed-meshheading:11520807-Flow Cytometry,
pubmed-meshheading:11520807-Genes, ras,
pubmed-meshheading:11520807-Humans,
pubmed-meshheading:11520807-Immunophenotyping,
pubmed-meshheading:11520807-Male,
pubmed-meshheading:11520807-Multiple Myeloma,
pubmed-meshheading:11520807-Mutation,
pubmed-meshheading:11520807-Mutation, Missense,
pubmed-meshheading:11520807-Neoplastic Stem Cells,
pubmed-meshheading:11520807-Point Mutation,
pubmed-meshheading:11520807-Polymerase Chain Reaction,
pubmed-meshheading:11520807-Polymorphism, Restriction Fragment Length,
pubmed-meshheading:11520807-Proto-Oncogene Proteins,
pubmed-meshheading:11520807-Proto-Oncogene Proteins c-bcl-6,
pubmed-meshheading:11520807-Transcription Factors
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pubmed:year |
2001
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pubmed:articleTitle |
Detection of N-Ras codon 61 mutations in subpopulations of tumor cells in multiple myeloma at presentation.
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pubmed:affiliation |
CRC Gene Regulation Group, Paterson Institute for Cancer Research, and CRC Department of Medical Oncology, Christie Hospital NHS Trust, Manchester, United Kingdom.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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