title: Further delineation of chromosomal consensus regions in primary mediastinal B-cell lymphomas: an analysis of 37 tumor samples using high-resolution genomic profiling (array-CGH).
abstract: Primary mediastinal B-cell lymphoma (PMBL) is an aggressive extranodal B-cell non-Hodgkin's lymphoma with specific clinical, histopathological and genomic features. To characterize further the genotype of PMBL, we analyzed 37 tumor samples and PMBL cell lines Med-B1 and Karpas1106P using array-based comparative genomic hybridization (matrix- or array-CGH) to a 2.8k genomic microarray. Due to a higher genomic resolution, we identified altered chromosomal regions in much higher frequencies compared with standard CGH: for example, +9p24 (68%), +2p15 (51%), +7q22 (32%), +9q34 (32%), +11q23 (18%), +12q (30%) and +18q21 (24%). Moreover, previously unknown small interstitial chromosomal low copy number alterations (for example, -6p21, -11q13.3) and a total of 19 DNA amplifications were identified by array-CGH. For 17 chromosomal localizations (10 gains and 7 losses), which were altered in more than 10% of the analyzed cases, we delineated minimal consensus regions based on genomic base pair positions. These regions and selected immunohistochemistries point to candidate genes that are discussed in the context of NF-kappaB transcription activation, human leukocyte antigen class I/II defects, impaired apoptosis and Janus kinase/signal transducer and activator of transcription (JAK/STAT) activation. Our data confirm the genomic uniqueness of this tumor and provide physically mapped genomic regions of interest for focused candidate gene analysis.
authors.affiliation: Klinik für Innere Medizin III, Zentrum für Innere Medizin der Universität Ulm, Ulm, Germany. swen.wessendorf@uniklinik-ulm.de
authors.forename: S
authors.initials: S
authors.lastname: Wessendorf
authors.forename: T F E
authors.initials: TF
authors.lastname: Barth
authors.forename: A
authors.initials: A
authors.lastname: Viardot
authors.forename: A
authors.initials: A
authors.lastname: Mueller
authors.forename: H A
authors.initials: HA
authors.lastname: Kestler
authors.forename: H
authors.initials: H
authors.lastname: Kohlhammer
authors.forename: P
authors.initials: P
authors.lastname: Lichter
authors.forename: M
authors.initials: M
authors.lastname: Bentz
authors.forename: H
authors.initials: H
authors.lastname: Döhner
authors.forename: P
authors.initials: P
authors.lastname: Möller
authors.forename: C
authors.initials: C
authors.lastname: Schwaenen
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor / Q000378:metabolism; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D016384:Consensus Sequence; D005260:Female; D005784:Gene Amplification; D017353:Gene Deletion; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053612:Janus Kinases / Q000235:genetics / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000473:pathology; D008297:Male; D008479:Mediastinal Neoplasms / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D050791:STAT Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D009363:Neoplasm Proteins; D050791:STAT Transcription Factors; D053612:Janus Kinases