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Activating Mutations of Nand Kras in Multiple Myeloma Show Different Clinical Associations : Analysis of the Eastern Cooperative Oncology Group Phase I 11 Trial

Mutations of members of the rasfamily are among the most common oncogene mutations found in multiple myeloma (MM). We have examined the mutational status of the Nand K-res genes at codons 12,13, and 61 in 160 newly diagnosed MM patients enrolled on the Eastern Cooperative Oncology Group (ECOG) phase 111 clinical trial E9486. The total incidence of ras mutations was found to be 39% of the samples analyzed. Five patients showed evidence of more than one mutation. We obtained 22 marrow samples from patients at the time of disease progression or relapse, for whom a res mutation was identified at diagnosis. In all cases, the ras mutation of the disease progression sample was identical t o that found at diagnosis. In contrast, three of 25 patients who did not show any ras mutation at diagnosis acquired a ras mutation at the time of disease progression. No significant association was observed between any ras mutation and stage of disease, &-microglobulin levels, labeling index, or protein type. The mean tumor burden and median survival for patients with mutations of N-ras was