Microarray-based genomic profiling reveals novel genomic aberrations in follicular lymphoma which associate with patient survival and gene expression status.
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Schwaenen Carsten, Viardot Andreas, Berger Hilmar, Barth Thomas F E, Bentink Stefan, Döhner Hartmut, Enz Martina, Feller Alfred C, Hansmann Martin-Leo, Hummel Michael, Kestler Hans A, Klapper Wolfram, Kreuz Markus, Lenze Dido, Loeffler Markus, Möller Peter, Müller-Hermelink Hans-Konrad, Ott German, Rosolowski Maciej, Rosenwald Andreas, Ruf Sandra, Siebert Reiner, Spang Rainer, Stein Harald, Truemper Lorenz, Lichter Peter, Bentz Martin, Wessendorf Swen, Molecular Mechanisms in Malignant Lymphomas Network Project of the Deutsche Krebshilfe
Аннотация
Follicular lymphoma (FL) is characterized by a large number of chromosomal aberrations. However, their exact genomic extension and involved target genes remain to be determined. For this purpose, we used array-based intermediate-high resolution genomic profiling in combination with Affymetrix gene expression analysis. Tumor specimens from 128 FL patients were analyzed for the presence of genomic aberrations and the results were correlated to clinical data sets and mRNA expression levels. In 114 (89%) of the 128 analyzed cases, a total of 688 genomic aberrations (384 gains/amplifications and 304 losses) were detected. Frequent genomic aberrations were: -1p36 (18%), +2p15 (24%), -3q (14%), -6q (25%), +7p (19%), +7q (23%), +8q (14%), -9p (16%), -11q (15%), +12q (20%), -13q (11%), -17p (16%), +18p (18%), and +18q (28%). Critical segments of these imbalances were delineated to genomic fragments with a minimum size down to 0.2 Mb. By comparison of these with mRNA gene expression data, putative candidate genes were identified. Moreover, we found that deletions affecting the tumor suppressor gene CDKN2A/B on 9p21 were detected in nontransformed FL grade I-II. For this aberration as well as for -6q25 and -6q26, an association with inferior survival was observed.