Detection of N-Ras codon 61 mutations in subpopulations of tumor cells in multiple myeloma at presentation.
AffiliationCRC Gene Regulation Group, Paterson Institute for Cancer Research, and CRC Department of Medical Oncology, Christie Hospital NHS Trust, Manchester, United Kingdom.
MetadataShow full item record
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.
CitationDetection of N-Ras codon 61 mutations in subpopulations of tumor cells in multiple myeloma at presentation. 2001, 98 (5):1555-60 Blood
- Activating mutations of N- and K-ras in multiple myeloma show different clinical associations: analysis of the Eastern Cooperative Oncology Group Phase III Trial.
- Authors: Liu P, Leong T, Quam L, Billadeau D, Kay NE, Greipp P, Kyle RA, Oken MM, Van Ness B
- Issue date: 1996 Oct 1
- N-ras and p53 gene mutations are very rare events in multiple myeloma.
- Authors: Yasuga Y, Hirosawa S, Yamamoto K, Tomiyama J, Nagata K, Aokia N
- Issue date: 1995 Aug
- Somatic mutation of the 5' noncoding region of the BCL-6 gene is associated with intraclonal diversity and clonal selection in histological transformation of follicular lymphoma.
- Authors: Szereday Z, Csernus B, Nagy M, László T, Warnke RA, Matolcsy A
- Issue date: 2000 Mar
- Ras oncogene mutation in multiple myeloma.
- Authors: Neri A, Murphy JP, Cro L, Ferrero D, Tarella C, Baldini L, Dalla-Favera R
- Issue date: 1989 Nov 1
- Oncogenes in multiple myeloma: point mutation of N-ras.
- Authors: Paquette RL, Berenson J, Lichtenstein A, McCormick F, Koeffler HP
- Issue date: 1990 Nov