Detection of N-Ras codon 61 mutations in subpopulations of tumor cells in multiple myeloma at presentation.

2.50
Hdl Handle:
http://hdl.handle.net/10541/84157
Title:
Detection of N-Ras codon 61 mutations in subpopulations of tumor cells in multiple myeloma at presentation.
Authors:
Kalakonda, Nagesh; Rothwell, Dominic G; Scarffe, J Howard; Norton, John D
Abstract:
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.
Affiliation:
CRC Gene Regulation Group, Paterson Institute for Cancer Research, and CRC Department of Medical Oncology, Christie Hospital NHS Trust, Manchester, United Kingdom.
Citation:
Detection of N-Ras codon 61 mutations in subpopulations of tumor cells in multiple myeloma at presentation. 2001, 98 (5):1555-60 Blood
Journal:
Blood
Issue Date:
1-Sep-2001
URI:
http://hdl.handle.net/10541/84157
PubMed ID:
11520807
Type:
Article
Language:
en
ISSN:
0006-4971
Appears in Collections:
All Christie Publications ; All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorKalakonda, Nageshen
dc.contributor.authorRothwell, Dominic Gen
dc.contributor.authorScarffe, J Howarden
dc.contributor.authorNorton, John Den
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.en
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

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