Analysis of ras gene mutations in childhood myeloid leukaemia

Abstract

Previous studies have shown that approximately 30% of adult acute myeloid leukaemias and 20% of adult acute lymphoid leukaemias contain point mutated ras oncogenes. In order to assess whether ras oncogenes are also involved in childhood leukaemias, we have used polymerase chain reaction (PCR) amplification and synthetic oligonucleotide probes to study the nature and frequency of ras gene mutations in childhood leukaemias, concentrating largely on the acute myeloid leukaemias (AML). Thirty-four childhood presentation AML DNAs were screened for mutations in and around codons 12, 61 and 117 of N-, K- and H-ras. Eight of these samples (24%) contained ras mutations. As in the adult disease, the gene predominantly involved was N-ras (6/8), with occasional activation of K-ras (2/6). The most common base change was a G----A transition at codon 12 or 13 (4/8). Of the patients with mutant ras, 4/8 were diagnosed as AML FAB subtype M5. Five of the 34 childhood AMLs analysed displayed abnormalities of chromosome 7. However, none of these cases contained a mutant ras gene. One AML patient was studied at relapse, 14 months after initial presentation. The presentation mutation (N61p3) was not detectable, although a new mutation (N13Cys) was readily identified. This observation extends our original finding with presentation and relapse samples of adult AML, in which it was uncommon for the relapse sample to contain the same ras mutation as the presentation DNA. In addition, two out of five patients diagnosed as juvenile CML, were found to harbour mutant ras.