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

Jennifer Edelmann, Karlheinz Holzmann, Florian Miller, Dirk Winkler, Andreas Bühler, Thorsten Zenz, Lars Bullinger, Michael W. M. Kühn, Andreas Gerhardinger, Johannes Bloehdorn, Ina Radtke, Xiaoping Su, Jing Ma, Stanley Pounds, Michael Hallek, Peter Lichter, Jan Korbel, Raymonde Busch, Daniel Mertens, James R. Downing, Stephan Stilgenbauer and Hartmut Döhner


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.