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High-resolution comparative genomic hybridisation yields a high detection rate of chromosomal aberrations in childhood acute lymphoblastic leukaemia

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Kristensen TD, Wesenberg F, Jonsson OG, Carlsen NT, Forestier E, Kirchhoff M, Lundsteen C, Schmiegelow K. High-resolution comparative genomic hybridisation yields a high detection rate of chromosomal aberrations in childhood acute lymphoblastic leukaemia. Eur J Haematol 2003: 70: 363–372. © Blackwell Munksgaard 2003. Abstract: Background:

Cytogenetic aberrations are of prognostic significance in childhood acute lymphoblastic leukaemias and a high detection rate could improve the biological understanding and classification of these diseases. Methods:

Bone-marrow samples from 92 children with acute lymphoblastic leukaemia were studied by high-resolution comparative genomic hybridisation (HRCGH) using dynamic standard reference intervals that enhance both specificity and sensitivity in the detection of aberrations. Results:

In 80 patients (87%) HRCGH revealed a total of 405 aberrations, mostly whole chromosome gains (n = 265) and partial losses (n = 80). The 25 leukaemias with a gain of more than five whole chromosomes by HRCGH harboured only 7% of all losses. With G-band karyotyping 59 patients (64%) had aberrations. HRCGH revealed more aberrations per patient than did G-band karyotyping (median: 3 vs. 1, P = 0.005), revealed aberrations in 27 of the 34 patients for whom the G-band karyotyping failed or was found to be normal, and specifically revealed more 9p losses (21% vs. 5%, P < 0.005), 12p losses (12% vs. 2%, P < 0.05) and 17q gains (11% vs. 1%, P < 0.01). Compared to the present study, the frequency of patients with aberrant karyotypes was significantly lower in previous conventional CGH studies (64% vs. 87%, P < 0.0001), as was the rate of partial aberrations per patient (1.1% vs. 1.7, P < 0.001), particularly with fewer 6q losses, 9p losses and 17q gains detected. Conclusion:

HRCGH is superior to conventional CGH as an adjunct to G-band karyotyping as it detects recurrent aberrations at a significantly higher rate than both these techniques.
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Keywords: acute lymphocytic leukaemia; comparative genomic hybridisation

Document Type: Research Article

Affiliations: 1: Department of Pediatrics, The University Hospital, Rigshospitalet, Copenhagen, Denmark; 2: Department of Pediatrics, The University Hospital, Rikshospitalet, Oslo, Norway; 3: Department of Pediatrics, The University Hospital, Reykjavik, Iceland; 4: Department of Pediatrics, The University Hospital, Odense, Denmark; 5: Department of Pediatrics, The University Hospital, Umeå, Sweden; and 6: Clinical Genetics, The University Hospital, Rigshospitalet, Copenhagen, Denmark

Publication date: June 1, 2003

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