Microsatellite analysis in childhood acute lymphoblastic leukemia

Abstract

BACKGROUND AND OBJECTIVE: Genetic alterations, including genomic instability, represent possible steps towards a malignant transformation. One approach to delineate replication errors in cancer cells is to determine alterations of microsatellites that are short tandem repeat sequences dispersed throughout the human genome. We have investigated whether genomic instability may be a possible event in the leukemogenic process by evaluating the pattern of instability in 41 cases of childhood acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: Eighty-two samples of genomic DNA (41 at diagnosis and 41 at remission) were analyzed by PCR with microsatellite markers chosen on five different chromosomes (2, 10, 11, 13, 18) known to be frequently involved in tumors of various origins. Since deletions of the short arm of chromosome 12 are relatively common in children with ALL, we also analyzed one region flanked by the microsatellite marker D12S308 on 12p. This area encompasses a genetic locus which contains the putative suppressor gene KIP1. RESULTS: A pattern of MI at one or two loci on different chromosomes could be documented in 4 of the 41 cases analyzed (9.7%). Three were common ALL and 1 was a T-ALL. One case showed two concomitant sites of instability, while 1 revealed two additional bands by using simultaneously microsatellite markers D2S123 and D18S58. INTERPRETATION AND CONCLUSIONS: These results indicate that genetic instability of microsatellite repeat sequences occurs in a proportion of childhood ALL. Mismatched repair errors documented in hereditary and sporadic solid tumors may thus be involved in hematological malignancies. While in such cases the pattern of genomic instability appears indicative of a mutator phenotype and of a potential predisposition towards a leukemic transformation, other genomic loci close to cytogenetic and molecular alterations known to occur in ALL need to be investigated in depth in cases with an apparently non mutated phenotype.