Automated array-based genomic profiling in chronic lymphocytic leukemia: development of a clinical tool and discovery of recurrent genomic alterations

Proc Natl Acad Sci U S A. 2004 Jan 27;101(4):1039-44. doi: 10.1073/pnas.0304717101. Epub 2004 Jan 16.


B cell chronic lymphocytic leukemia (B-CLL) is characterized by a highly variable clinical course. Recurrent chromosomal imbalances provide significant prognostic markers. Risk-adapted therapy based on genomic alterations has become an option that is currently being tested in clinical trials. To supply a robust tool for such large scale studies, we developed a comprehensive DNA microarray dedicated to the automated analysis of recurrent genomic imbalances in B-CLL by array-based comparative genomic hybridization (matrix-CGH). Validation of this chip in a series of 106 B-CLL cases revealed a high specificity and sensitivity that fulfils the criteria for application in clinical oncology. This chip is immediately applicable within clinical B-CLL treatment trials that evaluate whether B-CLL cases with distinct chromosomal abnormalities should be treated with chemotherapy of different intensities and/or stem cell transplantation. Through the control set of DNA fragments equally distributed over the genome, recurrent genomic imbalances were discovered: trisomy of chromosome 19 and gain of the MYCN oncogene correlating with an elevation of MYCN mRNA expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Automation
  • Base Sequence
  • DNA Primers
  • Gene Expression Profiling*
  • Genomics*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
  • N-Myc Proto-Oncogene Protein
  • Nuclear Proteins / genetics
  • Oncogene Proteins / genetics
  • RNA, Messenger / genetics
  • Sensitivity and Specificity


  • DNA Primers
  • MYCN protein, human
  • N-Myc Proto-Oncogene Protein
  • Nuclear Proteins
  • Oncogene Proteins
  • RNA, Messenger