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Mutational activation of N- and K-ras oncogenes in plasma cell dyscrasias
P Corradini, M Ladetto, C Voena, A Palumbo, G Inghirami, DM Knowles, M Boccadoro and A Pileri
Department of Medicine and Experimental Oncology, University of Torino,
Italy.
The frequency of N- and K-ras oncogene mutations was investigated in plasma
cell dyscrasias. Genomic DNAs from 128 patients were selected for this
study: 30 monoclonal gammopathies of undetermined significance, 8 solitary
plasmacytomas, 77 multiple myelomas (MM), and 13 plasma cell leukemias
(PCL). A two-step experimental approach was devised. All samples were
screened for mutations by single-strand conformation polymorphism analysis.
DNA fragments displaying an altered electrophoretic mobility were further
studied by direct sequencing to confirm and characterize the nature of the
mutations. Ras mutations are not randomly distributed because they are
detectable only in MM (9%) and PCL (30.7%). N-ras codons 12, 13, and 61 and
K-ras codon 12 were found to be mutated, but N-ras codon 61 mutation was
the most frequent finding (63.6%). In conclusion, ras mutations were found
in PCL, and in a subset of MM characterized by advanced-stage disease and
adverse prognostic parameters. Furthermore, based on our findings, it is
possible to speculate that ras mutations represent a late molecular lesion
in the process of multistep carcinogenesis.
Volume 81,
Issue 10,
pp. 2708-2713,
05/15/1993
Copyright © 1993 by The American Society of Hematology
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