Universität zu Köln

Edelmann, Jennifer, Holzmann, Karlheinz, Miller, Florian, Winkler, Dirk, Buehler, Andreas, Zenz, Thorsten, Bullinger, Lars ORCID: 0000-0002-5890-5510, Kuehn, Michael W. M., Gerhardinger, Andreas, Bloehdorn, Johannes, Radtke, Ina, Su, Xiaoping, Ma, Jing, Pounds, Stanley, Hallek, Michael, Lichter, Peter, Korbel, Jan, Busch, Raymonde, Mertens, Daniel ORCID: 0000-0003-0227-7188, Downing, James R., Stilgenbauer, Stephan and Doehner, Hartmut (2012). High-resolution genomic profiling of chronic lymphocytic leukemia reveals new recurrent genomic alterations. Blood, 120 (24). S. 4783 - 4795. WASHINGTON: AMER SOC HEMATOLOGY. ISSN 0006-4971

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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. (Blood. 2012;120(24):4783-4794)

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Edelmann, Jennifer UNSPECIFIED UNSPECIFIED UNSPECIFIED Holzmann, Karlheinz UNSPECIFIED UNSPECIFIED UNSPECIFIED Miller, Florian UNSPECIFIED UNSPECIFIED UNSPECIFIED Winkler, Dirk UNSPECIFIED UNSPECIFIED UNSPECIFIED Buehler, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Zenz, Thorsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Bullinger, Lars UNSPECIFIED orcid.org/0000-0002-5890-5510 UNSPECIFIED Kuehn, Michael W. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gerhardinger, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Bloehdorn, Johannes UNSPECIFIED UNSPECIFIED UNSPECIFIED Radtke, Ina UNSPECIFIED UNSPECIFIED UNSPECIFIED Su, Xiaoping UNSPECIFIED UNSPECIFIED UNSPECIFIED Ma, Jing UNSPECIFIED UNSPECIFIED UNSPECIFIED Pounds, Stanley UNSPECIFIED UNSPECIFIED UNSPECIFIED Hallek, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Lichter, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Korbel, Jan UNSPECIFIED UNSPECIFIED UNSPECIFIED Busch, Raymonde UNSPECIFIED UNSPECIFIED UNSPECIFIED Mertens, Daniel UNSPECIFIED orcid.org/0000-0003-0227-7188 UNSPECIFIED Downing, James R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Stilgenbauer, Stephan UNSPECIFIED UNSPECIFIED UNSPECIFIED Doehner, Hartmut UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-476884
DOI:	10.1182/blood-2012-04-423517
Journal or Publication Title:	Blood
Volume:	120
Number:	24
Page Range:	S. 4783 - 4795
Date:	2012
Publisher:	AMER SOC HEMATOLOGY
Place of Publication:	WASHINGTON
ISSN:	0006-4971
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ACUTE LYMPHOBLASTIC-LEUKEMIA; GENETIC ALTERATIONS; CHROMOSOME 13Q14; POOR-PROGNOSIS; WIDE ANALYSIS; FOLLOW-UP; MYC; FLUDARABINE; MUTATIONS; DELETION Multiple languages Hematology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/47688