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.
- Copyright © 2005 American Society of Hematology