Structural and numerical abnormalities resolved in one-step analysis: the most common chromosomal rearrangements detected by comparative genomic hybridization in childhood acute lymphoblastic leukemia

Abstract

Comparative genomic hybridization (CGH) is a technique that permits detection of chromosomal imbalances. This method allows the detection of gains and losses of genetic material at a resolution lower than 5 Mb. The limitations of conventional cytogenetic studies, such as morphologically insufficient quality of metaphases or the mitotic index, can be eliminated by use of CGH. It is particularly important in the diagnosis of leukemias, and CGH could be a useful tool enabling more precise cytogenetic analysis of leukemic cells. A group of 89 children with acute lymphoblastic leukemia was studied by means of CGH using bone marrow obtained from all consecutive pediatric patients. CGH experiments were performed according to the manufacturer's instruction with minor modifications. In addition, each sample was examined with standard GTG technique and fluorescence in situ hybridization. The conventional cytogenetics failed in 12 patients (13.5%), and 22 patients (24.7%) had a normal karyotype. Structural and numerical changes were found in 55 cases (61.8%) displaying a different abnormalities including deletions, trisomies, tetrasomies, isochromosomes, and markers with unknown origin. However, all samples were successfully analyzed by CGH. We have shown that high-resolution comparative genomic hybridization analysis is a reliable and relatively quick one-step method to identify main aberrations that would not be detected by either conventional G banding or by conventional fluorescence in situ hybridization. It should be considered to establish CGH as a routine analysis for screening patients with acute lymphoblastic leukemia.