Efficacy of high-resolution comparative genomic hybridization (HR-CGH) in detection of chromosomal abnormalities in children with acute leukaemia

• Published in: Neoplasma Vol. 55; no. 1; p. 23
• Main Authors: Vranova, V, Mentzlova, D, Oltova, A, Linkova, V, Zezulkova, D, Filkova, H, Mendelova, D, Sterba, J, Kuglik, P
• Format: Journal Article
• Language: English
• Published: Slovakia 2008
• Subjects: Acute Disease; Adolescent; Child; Child, Preschool; Chromosome Aberrations; Chromosome Banding; Female; Humans; In Situ Hybridization, Fluorescence; Infant; Leukemia - genetics; Male; Nucleic Acid Hybridization - methods
• ISSN: 0028-2685

The efficient detection of chromosomal aberrations in childhood acute leukaemias presents a significant component in the diagnostics of this frequent malignant disease. We used comparative genomic hybridization (CGH) and high-resolution comparative genomic hybridization (HR-CGH) to determine the frequency of chromosomal changes in 33 children with acute leukaemia (AL). The yields of chromosomal abnormalities were compared with the results obtained using conventional cytogenetics (G-banding) and fluorescence in situ hybridization (FISH). Conventional cytogenetics revealed chromosomal changes in 17 (52 %) of studied patients. The employment of FISH together with G-banding analysis identified chromosomal changes in 27 (82 %) of the AL patients investigated. CGH detected changes in DNA copy numbers in 24 (73 %) patients, 40 losses and 67 gains were found in total. HR-CGH disclosed 98 losses and 97 gains in 26 (79 %) patients. In comparison with CGH, HR-CGH analyses unveiled 88 new chromosomal aberrations: 58 losses and 30 gains. The most commonly gained chromosomes were 21 (22.5 %), X (15 %), 18 (12,5 %) and 17 (10 %). The most common losses involved sub-regions or arms of chromosomes 7 (15 %), 9 (12.5 %), 16, 19 and 1 (10 % each). Cytogenetic and molecular cytogenetic analyses of 33 childhood acute leukaemias revealed chromosomal changes in total 31 (94 %) patients. The evaluation of HR-CGH sensitivity proved that the minimal cell population of malignant cells in which a certain chromosomal change could be found was close to the 20 - 30 % level. Our results confirm the benefits of HR-CGH in detecting chromosomal changes in childhood AL. Supplementing G-banding and FISH with the HR-CGH diagnostic method increases the detection of unbalanced structural chromosomal rearrangements and can reveal small cell clones with gains and losses of whole chromosomes in hyperdiploid AL.