Efficacy of high - resolution comparative genomic hybridization in detection of chromosomal abnormalities in children with acute leukemia.

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Authors

VRANOVÁ Vladimíra MENTZLOVÁ Dita OLTOVÁ Alexandra LINKOVÁ Vlasta ŽEŽULKOVÁ Dita FILKOVÁ Hana MENDELOVÁ Denisa ŠTĚRBA Jaroslav KUGLÍK Petr

Year of publication 2008
Type Article in Periodical
Magazine / Source Neoplasma
MU Faculty or unit

Faculty of Medicine

Citation
Field Genetics and molecular biology
Keywords comparative genomic hybridization (CGH); high resolution comparative genomic hybridization (HRCGH); chromosomal aberrations; acute myeloid leukaemia; acute lymphoid leukaemia
Description 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 (HRCGH) 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. HRCGH 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 subregions 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 HRCGH sensitivity proved that the minimal cell population of malignant cells in which a certain chromosomal change could be found was close to the 20 to 30 % level. Our results confirm the benefits of HRCGH 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.
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