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Automated array-based genomic profiling in chronic lymphocytic leukemia: development of a clinical tool and discovery of recurrent genomic alterations.

Authors
  • Schwaenen, Carsten
  • Nessling, Michelle
  • Wessendorf, Swen
  • Salvi, Tatjana
  • Wrobel, Gunnar
  • Radlwimmer, Bernhard
  • Kestler, Hans A
  • Haslinger, Christian
  • Stilgenbauer, Stephan
  • Döhner, Hartmut
  • Bentz, Martin
  • Lichter, Peter
Type
Published Article
Journal
Proceedings of the National Academy of Sciences of the United States of America
Publication Date
Jan 27, 2004
Volume
101
Issue
4
Pages
1039–1044
Identifiers
PMID: 14730057
Source
Medline
License
Unknown

Abstract

B cell chronic lymphocytic leukemia (B-CLL) is characterized by a highly variable clinical course. Recurrent chromosomal imbalances provide significant prognostic markers. Risk-adapted therapy based on genomic alterations has become an option that is currently being tested in clinical trials. To supply a robust tool for such large scale studies, we developed a comprehensive DNA microarray dedicated to the automated analysis of recurrent genomic imbalances in B-CLL by array-based comparative genomic hybridization (matrix-CGH). Validation of this chip in a series of 106 B-CLL cases revealed a high specificity and sensitivity that fulfils the criteria for application in clinical oncology. This chip is immediately applicable within clinical B-CLL treatment trials that evaluate whether B-CLL cases with distinct chromosomal abnormalities should be treated with chemotherapy of different intensities and/or stem cell transplantation. Through the control set of DNA fragments equally distributed over the genome, recurrent genomic imbalances were discovered: trisomy of chromosome 19 and gain of the MYCN oncogene correlating with an elevation of MYCN mRNA expression.

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