title: High-resolution genomic profiling of chronic lymphocytic leukemia reveals new recurrent genomic alterations.
abstract: To identify genomic alterations in chronic lymphocytic leukemia (CLL), we performed single-nucleotide polymorphism-array analysis using Affymetrix Version 6.0 on 353 samples from untreated patients entered in the CLL8 treatment trial. Based on paired-sample analysis (n = 144), a mean of 1.8 copy number alterations per patient were identified; approximately 60% of patients carried no copy number alterations other than those detected by fluorescence in situ hybridization analysis. Copy-neutral loss-of-heterozygosity was detected in 6% of CLL patients and was found most frequently on 13q, 17p, and 11q. Minimally deleted regions were refined on 13q14 (deleted in 61% of patients) to the DLEU1 and DLEU2 genes, on 11q22.3 (27% of patients) to ATM, on 2p16.1-2p15 (gained in 7% of patients) to a 1.9-Mb fragment containing 9 genes, and on 8q24.21 (5% of patients) to a segment 486 kb proximal to the MYC locus. 13q deletions exhibited proximal and distal breakpoint cluster regions. Among the most common novel lesions were deletions at 15q15.1 (4% of patients), 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 CLL patient 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 deleted recurrently.
authors.affiliation: Department of Internal Medicine III, Ulm University, Ulm, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Edelmann
authors.forename: Karlheinz
authors.initials: K
authors.lastname: Holzmann
authors.forename: Florian
authors.initials: F
authors.lastname: Miller
authors.forename: Dirk
authors.initials: D
authors.lastname: Winkler
authors.forename: Andreas
authors.initials: A
authors.lastname: Bühler
authors.forename: Thorsten
authors.initials: T
authors.lastname: Zenz
authors.forename: Lars
authors.initials: L
authors.lastname: Bullinger
authors.forename: Michael W M
authors.initials: MW
authors.lastname: Kühn
authors.forename: Andreas
authors.initials: A
authors.lastname: Gerhardinger
authors.forename: Johannes
authors.initials: J
authors.lastname: Bloehdorn
authors.forename: Ina
authors.initials: I
authors.lastname: Radtke
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Su
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.forename: Stanley
authors.initials: S
authors.lastname: Pounds
authors.forename: Michael
authors.initials: M
authors.lastname: Hallek
authors.forename: Peter
authors.initials: P
authors.lastname: Lichter
authors.forename: Jan
authors.initials: J
authors.lastname: Korbel
authors.forename: Raymonde
authors.initials: R
authors.lastname: Busch
authors.forename: Daniel
authors.initials: D
authors.lastname: Mertens
authors.forename: James R
authors.initials: JR
authors.lastname: Downing
authors.forename: Stephan
authors.initials: S
authors.lastname: Stilgenbauer
authors.forename: Hartmut
authors.initials: H
authors.lastname: Döhner
mesh_terms: D002869:Chromosome Aberrations; D056915:DNA Copy Number Variations; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D023281:Genomics / Q000379:methods*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D019656:Loss of Heterozygosity; D008297:Male; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D016159:Tumor Suppressor Protein p53