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dc.contributor.authorKalakonda, Nagesh
dc.contributor.authorRothwell, Dominic G
dc.contributor.authorScarffe, J Howard
dc.contributor.authorNorton, John D
dc.date.accessioned2009-10-13T10:32:43Z
dc.date.available2009-10-13T10:32:43Z
dc.date.issued2001-09-01
dc.identifier.citationDetection of N-Ras codon 61 mutations in subpopulations of tumor cells in multiple myeloma at presentation. 2001, 98 (5):1555-60 Blooden
dc.identifier.issn0006-4971
dc.identifier.pmid11520807
dc.identifier.urihttp://hdl.handle.net/10541/84157
dc.description.abstractActivating 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.
dc.language.isoenen
dc.subjectCancer DNAen
dc.subjectCancer Stem Cellsen
dc.subject.mesh5' Untranslated Regions
dc.subject.meshAmino Acid Substitution
dc.subject.meshCell Separation
dc.subject.meshCell Transformation, Neoplastic
dc.subject.meshClone Cells
dc.subject.meshCodon
dc.subject.meshDNA Mutational Analysis
dc.subject.meshDNA, Neoplasm
dc.subject.meshDNA-Binding Proteins
dc.subject.meshFemale
dc.subject.meshFlow Cytometry
dc.subject.meshGenes, ras
dc.subject.meshHumans
dc.subject.meshImmunophenotyping
dc.subject.meshMale
dc.subject.meshMultiple Myeloma
dc.subject.meshMutation
dc.subject.meshMutation, Missense
dc.subject.meshNeoplastic Stem Cells
dc.subject.meshPoint Mutation
dc.subject.meshPolymerase Chain Reaction
dc.subject.meshPolymorphism, Restriction Fragment Length
dc.subject.meshProto-Oncogene Proteins
dc.subject.meshProto-Oncogene Proteins c-bcl-6
dc.subject.meshTranscription Factors
dc.titleDetection of N-Ras codon 61 mutations in subpopulations of tumor cells in multiple myeloma at presentation.en
dc.typeArticleen
dc.contributor.departmentCRC Gene Regulation Group, Paterson Institute for Cancer Research, and CRC Department of Medical Oncology, Christie Hospital NHS Trust, Manchester, United Kingdom.en
dc.identifier.journalBlooden
html.description.abstractActivating 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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