High incidence of N and K-Ras activating mutations in multiple myeloma and primary plasma cell leukemia at diagnosis
Article first published online: 22 AUG 2001
Copyright © 2001 Wiley-Liss, Inc.
Volume 18, Issue 3, pages 212–224, September 2001
How to Cite
Bezieau, S., Devilder, M.-C., Avet-Loiseau, H., Mellerin, M.-P., Puthier, D., Pennarun, E., Rapp, M.-J., Harousseau, J.-L., Moisan, J.-P. and Bataille, R. (2001), High incidence of N and K-Ras activating mutations in multiple myeloma and primary plasma cell leukemia at diagnosis. Hum. Mutat., 18: 212–224. doi: 10.1002/humu.1177
- Issue published online: 22 AUG 2001
- Article first published online: 22 AUG 2001
- Manuscript Accepted: 4 MAY 2001
- Manuscript Received: 27 FEB 2001
- multiple myeloma;
- plasma-cell leukemia;
- mutation detection
Using allele-specific amplification method (ARMS), a highly sensitive one-stage allele-specific PCR, we have evaluated the incidence of NRAS and KRAS2 activating mutations (codons 12, 13, and 61) in 62 patients with either monoclonal gammopathy of undetermined significance (MGUS) or multiple myeloma (MM), primary plasma-cell leukemia (P-PCL), and also in human myeloma cell lines (HMCL). NRAS and/or KRAS2 mutations were found in 54.5% of MM at diagnosis (but in 81% at the time of relapse), in 50% of P-PCL, and in 50% of 16 HMCL. In contrast, the occurrence of such mutations was very low in MGUS and indolent MM (12.50%). Of note, KRAS2 mutations were always more frequent than NRAS. The validity of the technique was assessed by direct sequencing of cell lines and of some patients. Multiple mutations found in two patients were confirmed by subcloning exon PCR amplification products, testing clones with our method, and sequencing them. Thus, these early mutations could play a major role in the oncogenesis of MM and P-PCL. Hum Mutat 18:212–224, 2001. © 2001 Wiley-Liss, Inc.