ras Mutations in the Myelodysplastic Syndromes

The ras gene family—H-ras, K-ras and N-ras— code for 21-kDa proteins that have GTPase activity and have been implicated in the control of cell proliferation [8,13]. Mutations in these genes give rise to abnormal protein products that have the capacity to transform certain cells to a malignant phenotype. The ras mutations have been found in a wide range of human malignancies, and N-ras has been particularly implicated in acute myeloid leukaemia (AML), chronic myeloid leukaemia and acute lymphoblastic leukaemia [4, 5]. Activation of these genes has been associated with mutations in codons 12/13 or codon 61, and lesions of this type have recently been described in myelodysplastic syndromes (MDS). Hirai et al. [3] described three MDS patients with codon 13 mutations in N-ras,and Liu et al. [6] reported two patients with a similar mutation in K-ras. We have assessed the mutational status of members of the ras gene family by polymerase chain reaction and hybridisation with synthetic oligonucleotide probes in 50 patients with MDS together with the use of a nude mouse tumorgenicity assay in some cases [9].