ANALYSIS OF MUTATIONS AT THE DNA-REPAIR GENES IN ACUTE CHILDHOOD LEUKEMIA

Deficiency in DNA repair capability is considered to be responsible fo r oncogenesis. Hereditary and sporadic cancers in various tissues have been reported to have mutations at the DNA repair genes. In this stud y we analysed two excision repair genes (ERCC1 and XPCC) and two misma tch repair genes (hMSH2 and hMTH1) in the leukaemic blasts of newly di agnosed paediatric patients by use of reverse transcriptase (RT)-polym erase chain reaction (PCR). Analysis of the leukaemic blasts from 15 p atients demonstrated no alterations at the XPCC, hMSH2 or hMTH1 genes. Blasts from one patient with acute mixed lineage leukaemia revealed a n abnormally migrated product of the ERCC1 gene by RT-PCR. His leukaem ic blasts showed a reduced expression of ERCC1 protein by Western blot ting. Since bone marrow cells at remission showed only normally migrat ed product, the ERCC1 gene mutation was considered to be specific for the leukaemic blasts. This is the first report describing a mutation a t the ERCC1 gene in acute childhood leukaemia.