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) ha ve been thought to be involved in carcinogenesis, but have not been investi gated in childhood leukemia and lymphoma. Methods: Eighty samples from 65 patients with childhood leukemia and lympho ma were examined using seven different microsatellite markers for RER analy sis. Additionally, LOH in two chromosome regions (9p and 12p) was investiga ted. Furthermore, expression of the TEL, TEL/AML1 and p27(KIP1) genes on 12 p 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. Ther e 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 fu sion gene on 12p and the other with common ALL and 12p RER had diminished e xpression 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 ac ute leukemia, especially in common ALL.