Analysis of mutations at the DNA repair genes in acute childhood leukaemia

Deficiency in DNA repair capability is considered to be responsible for oncogenesis. Hereditary and sporadic cancers in various tissues have been reported to have mutations at the DNA repair genes. In this study we analysed two excision repair genes (ERCC1 and XPCC) and two mismatch repair genes (hMSH2 and hMTH1) in the leukaemic blasts of newly diagnosed paediatric patients by use of reverse transcriptase (RT)–polymerase chain reaction (PCR). Analysis of the leukaemic blasts from 15 patients demonstrated no alterations at the XPCC, hMSH2 or hMTH1 genes. Blasts from one patient with acute mixed lineage leukaemia revealed an abnormally migrated product of the ERCC1 gene by RT-PCR. His leukaemic blasts showed a reduced expression of ERCC1 protein by Western blotting. Since bone marrow cells at remission showed only normally migrated product, the ERCC1 gene mutation was considered to be specific for the leukaemic blasts. This is the first report describing a mutation at the ERCC1 gene in acute childhood leukaemia.