Microsatellite analysis of childhood leukemia: Correlation of 9p and 12p chromosome abnormalities with expression of related genes

Background: Loss of heterozygosity (LOH) and DNA replication error (RER) have been thought to be involved in carcinogenesis, but have not been investigated in childhood leukemia and lymphoma. Methods: Eighty samples from 65 patients with childhood leukemia and lymphoma were examined using seven different microsatellite markers for RER analysis. Additionally, LOH in two chromosome regions (9p and 12p) was investigated. Furthermore, expression of the TEL, TEL/AML1 and p27(KIP1) genes on 12p and the p16 gene on 9p were detected by reverse transcriptase polymerase chain reaction. Results: Replication errors were detected in 5/65 patients (7.7%). Most (4/5 patients) RER were preferentially located in the 9p and 12p regions. There were two patients who had DNA abnormalities in both 9p and 12p, one with common acute lymphoblastic leukemia (ALL) showed 9p LOH and the TEL/AML1 fusion gene on 12p and the other with common ALL and 12p RER had diminished expression of both the p27(KIP1) gene on 12p and the p16 gene on 9p. Conclusions: Combined DNA alterations on 9p and 12p, involving LOH, RER and/or gene mutation and chromosomal translocation, were found in childhood acute leukemia, especially in common ALL.