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

Eur J Haematol. 2003 Jun;70(6):363-72. doi: 10.1034/j.1600-0609.2003.00072.x.

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.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Bone Marrow
  • Child
  • Child, Preschool
  • Chromosome Aberrations*
  • Female
  • Gene Dosage
  • Humans
  • Infant
  • Karyotyping
  • Male
  • Nucleic Acid Hybridization*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Reference Standards
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sensitivity and Specificity