RAS mutations in preleukaemias.

Activated ras genes have been implicated in a wide variety of neoplasms [2]. N-ras in particular has been shown to be involved in acute myelogenous leukaemia (AML) with activating mutations around codons 12/13 and 61 [3, 7]. The myelodysplastic syndromes (MDS) are a group of preleukaemias, a proportion of which will develop AML. Hirai et al. [9] described three MDS patients with N-ras mutations in codon 13 and Liu et al. [12] showed K-ras activations in two MDS patients. In this study we have screened DNA from peripheral blood or bone marrow of 50 MDS patients for ras mutations around codons 12/13 and 61 of H, K and N -ras and around codon 117 of N-ras. A mutation in position 117 of Hras has been reported to be an activating mutation in vivo in chemically induced murine liver tumours [15]. Mutations in codons 116-119 of H-ras have been shown to reduce the ability of the H-ras p21 protein to bind and hydrolyse guanosine triphosphate (GTP) and some of these mutations are capable of activating the transforming potential of the normal gene [5, 20]. U sing an amplification procedure called polymerase chain reaction (PCR) [16] and hybridisation with synthetic oligonucleotide probes [7, 21], ras mutations were detected in 20/50 (40%) MDS