2.50
Hdl Handle:
http://hdl.handle.net/10033/601039
Title:
Genomic Landscape of Primary Mediastinal B-Cell Lymphoma Cell Lines.
Authors:
Dai, Haiping; Ehrentraut, Stefan; Nagel, Stefan; Eberth, Sonja; Pommerenke, Claudia ( 0000-0002-9448-416X ) ; Dirks, Wilhelm G; Geffers, Robert ( 0000-0003-4409-016X ) ; Kalavalapalli, Srilaxmi; Kaufmann, Maren; Meyer, Corrina; Faehnrich, Silke; Chen, Suning; Drexler, Hans G; MacLeod, Roderick A F
Abstract:
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.
Affiliation:
Helmholtz Centre for infection research (HZI), Inhoffenstraße 7, 38124 Braunschweig, Germany.
Citation:
Genomic Landscape of Primary Mediastinal B-Cell Lymphoma Cell Lines. 2015, 10 (11):e0139663 PLoS ONE
Journal:
PloS one
Issue Date:
2015
URI:
http://hdl.handle.net/10033/601039
DOI:
10.1371/journal.pone.0139663
PubMed ID:
26599546
Type:
Article
Language:
en
ISSN:
1932-6203
Appears in Collections:
publications of the research group genomeanalytics (GMAK)

Full metadata record

DC FieldValue Language
dc.contributor.authorDai, Haipingen
dc.contributor.authorEhrentraut, Stefanen
dc.contributor.authorNagel, Stefanen
dc.contributor.authorEberth, Sonjaen
dc.contributor.authorPommerenke, Claudiaen
dc.contributor.authorDirks, Wilhelm Gen
dc.contributor.authorGeffers, Roberten
dc.contributor.authorKalavalapalli, Srilaxmien
dc.contributor.authorKaufmann, Marenen
dc.contributor.authorMeyer, Corrinaen
dc.contributor.authorFaehnrich, Silkeen
dc.contributor.authorChen, Suningen
dc.contributor.authorDrexler, Hans Gen
dc.contributor.authorMacLeod, Roderick A Fen
dc.date.accessioned2016-03-09T15:18:54Zen
dc.date.available2016-03-09T15:18:54Zen
dc.date.issued2015en
dc.identifier.citationGenomic Landscape of Primary Mediastinal B-Cell Lymphoma Cell Lines. 2015, 10 (11):e0139663 PLoS ONEen
dc.identifier.issn1932-6203en
dc.identifier.pmid26599546en
dc.identifier.doi10.1371/journal.pone.0139663en
dc.identifier.urihttp://hdl.handle.net/10033/601039en
dc.description.abstractPrimary 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.en
dc.language.isoenen
dc.titleGenomic Landscape of Primary Mediastinal B-Cell Lymphoma Cell Lines.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection research (HZI), Inhoffenstraße 7, 38124 Braunschweig, Germany.en
dc.identifier.journalPloS oneen

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