Blood Journal
Leading the way in experimental and clinical research in hematology

High-resolution genomic profiling of chronic lymphocytic leukemia reveals new recurrent genomic alterations

  1. Jennifer Edelmann1,
  2. Karlheinz Holzmann2,
  3. Florian Miller1,
  4. Dirk Winkler1,
  5. Andreas Bühler1,
  6. Thorsten Zenz3,
  7. Lars Bullinger1,
  8. Michael W. M. Kühn1,
  9. Andreas Gerhardinger2,
  10. Johannes Bloehdorn1,
  11. Ina Radtke4,
  12. Xiaoping Su4,
  13. Jing Ma5,
  14. Stanley Pounds5,
  15. Michael Hallek6,
  16. Peter Lichter7,
  17. Jan Korbel8,
  18. Raymonde Busch9,
  19. Daniel Mertens1,
  20. James R. Downing4,
  21. Stephan Stilgenbauer1, and
  22. Hartmut Döhner1,*
  1. 1 Department of Internal Medicine III, Ulm University, Ulm, Germany;
  2. 2 Interdisciplinary Center for Clinical Research, Genomics Core Facility, Ulm University, Ulm, Germany;
  3. 3 Department of Translational Oncology, National Center for Tumor Diseases and German Research Center, and Department of Medicine V, University of Heidelberg, Heidelberg, Germany;
  4. 4 Pathology, St. Jude Children's Hospital, Memphis, TN, United States;
  5. 5 Hartwell Center for Bioinformatics and Biotechnology, St. Jude Children's Hospital, Memphis, TN, United States;
  6. 6 Department of Internal Medicine I, University of Cologne, Cologne, Germany;
  7. 7 Division of Molecular Genetics, German Cancer Research Center, Heidelberg, Germany;
  8. 8 European Molecular Biology Laboratory, Heidelberg, Germany;
  9. 9 Institute of Medical Statistics and Epidemiology, Technical University, Munich, Germany
  1. * Corresponding author; email: hartmut.doehner{at}


To identify genomic alterations in chronic lymphocytic leukemia (CLL), we performed single-nucleotide polymorphism (SNP)-array analysis (Affymetrix 6.0) on 353 samples from untreated patients entered on the CLL8 treatment trial. Based on paired-sample analysis (n=144), a mean of 1.8 copy number alterations (CNAs) per case were identified; about 60% of cases carried no CNAs other than those detected by fluorescence in-situ hybridization analysis. Copy-neutral loss-of-heterozygosity was detected in 6% of cases, and most frequently found on 13q, 17p and 11q. Minimally deleted regions were refined on 13q14 (deleted in 61% of cases) to the DLEU1 and DLEU2 genes, on 11q22.3 (27%) to ATM, on 2p16.1-2p15 (gained in 7%) to a 1.9 Mb fragment containing 9 genes, and on 8q24.21 (5%) to a segment 486 Kb proximal of the MYC locus. 13q deletions exhibited proximal and distal breakpoint cluster regions. Among the most common novel lesions were deletions at 15q15.1 (4%), with the smallest deletion (70.48 Kb) found in the MGA locus. Sequence analysis of MGA in 59 samples revealed a truncating mutation in one case lacking a 15q deletion. MNT at 17p13.3, which in addition to MGA and MYC encodes for the network of MAX-interacting proteins, was also found recurrently deleted.

  • Submitted April 23, 2012.
  • Accepted September 23, 2012.