Genomic Landscape of Primary Mediastinal B-Cell Lymphoma Cell Lines.
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Authors
Dai, HaipingEhrentraut, Stefan
Nagel, Stefan
Eberth, Sonja
Pommerenke, Claudia

Dirks, Wilhelm G
Geffers, Robert

Kalavalapalli, Srilaxmi
Kaufmann, Maren
Meyer, Corrina
Faehnrich, Silke
Chen, Suning
Drexler, Hans G
MacLeod, Roderick A F
Issue Date
2015
Metadata
Show full item recordAbstract
Primary mediastinal B-Cell lymphoma (PMBL) is a recently defined entity comprising ~2-10% non-Hodgkin lymphomas (NHL). Unlike most NHL subtypes, PMBL lacks recurrent gene rearrangements to serve as biomarkers or betray target genes. While druggable, late chemotherapeutic complications warrant the search for new targets and models. Well characterized tumor cell lines provide unlimited material to serve as preclinical resources for verifiable analyses directed at the discovery of new biomarkers and pathological targets using high throughput microarray technologies. The same cells may then be used to seek intelligent therapies directed at clinically validated targets. Four cell lines have emerged as potential PMBL models: FARAGE, KARPAS-1106P, MEDB-1 and U-2940. Transcriptionally, PMBL cell lines cluster near c(lassical)-HL and B-NHL examples showing they are related but separate entities. Here we document genomic alterations therein, by cytogenetics and high density oligonucleotide/SNP microarrays and parse their impact by integrated global expression profiling. PMBL cell lines were distinguished by moderate chromosome rearrangement levels undercutting cHL, while lacking oncogene translocations seen in B-NHL. In total 61 deletions were shared by two or more cell lines, together with 12 amplifications (≥4x) and 72 homozygous regions. Integrated genomic and transcriptional profiling showed deletions to be the most important class of chromosome rearrangement. Lesions were mapped to several loci associated with PMBL, e.g. 2p15 (REL/COMMD1), 9p24 (JAK2, CD274), 16p13 (SOCS1, LITAF, CIITA); plus new or tenuously associated loci: 2p16 (MSH6), 6q23 (TNFAIP3), 9p22 (CDKN2A/B), 20p12 (PTPN1). Discrete homozygous regions sometimes substituted focal deletions accompanied by gene silencing implying a role for epigenetic or mutational inactivation. Genomic amplifications increasing gene expression or gene-activating rearrangements were respectively rare or absent. Our findings highlight biallelic deletions as a major class of chromosomal lesion in PMBL cell lines, while endorsing the latter as preclinical models for hunting and testing new biomarkers and actionable targets.Citation
Genomic Landscape of Primary Mediastinal B-Cell Lymphoma Cell Lines. 2015, 10 (11):e0139663 PLoS ONEAffiliation
Helmholtz Centre for infection research (HZI), Inhoffenstraße 7, 38124 Braunschweig, Germany.Journal
PloS onePubMed ID
26599546Type
ArticleLanguage
enISSN
1932-6203ae974a485f413a2113503eed53cd6c53
10.1371/journal.pone.0139663
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