Details

Autor(en) / Beteiligte

• 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

Titel

Automated Array-Based Genomic Profiling in Chronic Lymphocytic Leukemia: Development of a Clinical Tool and Discovery of Recurrent Genomic Alterations

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2004-01, Vol.101 (4), p.1039-1044

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2004

Quelle

EZB-FREE-00999 freely available EZB journals

Beschreibungen/Notizen

• 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.