Molecular and functional profiling of plasmablastic lymphoma

Plasmablastic lymphoma (PBL) represents a rare and aggressive lymphoma subtype frequently associated with immunosuppression. Clinically, patients with PBL are characterized by poor outcome. The current understanding of the molecular pathogenesis is limited. A hallmark of PBL represents its plasmacytic differentiation with loss of B-cell markers and, in 60% of cases, its association with Epstein-Barr virus (EBV). Roughly 50% of PBLs harbor a MYC translocation. Here, we provide a comprehensive integrated genomic analysis using whole exome sequencing (WES) and genome-wide copy number determination in a large cohort of 96 primary PBL samples. We identify alterations activating the RAS-RAF, JAK-STAT, and NOTCH pathways as well as frequent high-level amplifications in MCL1 and IRF4. The functional impact of these alterations is assessed using an unbiased shRNA screen in a PBL model. These analyses identify the IRF4 and JAK-STAT pathways as promising molecular targets to improve outcome of PBL patients.

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

2 Datasets 1 Publication

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID	Description	Technology	Samples
EGAD00001006400	1 cell line and 123 patient samples including 38 normal (22 paired normal and 16 unpaired), 85 tumor-initial, FASTQ file types, Agilent SureSelect Human All Exon V6 Kit	Illumina HiSeq 2500	124
EGAD00010001978	1 cell line and 82 Oncoscan SNP tumor initial samples, zipped Affymetrix CEL file types, Oncoscan CNV FFPE Assay Kit, Thermo Fisher Scientific GeneChipTM Scanner 3000 7G	Affymetrix, Thermo Fisher Scientific	85

Publications	Citations
Molecular and functional profiling identifies therapeutically targetable vulnerabilities in plasmablastic lymphoma. Frontzek F, Staiger AM, Zapukhlyak M, Xu W, Bonzheim I, Borgmann V, Sander P, Baptista MJ, Heming JN, Berning P, Wullenkord R, Erdmann T, Lutz M, Veratti P, Ehrenfeld S, Wienand K, Horn H, Goodlad JR, Wilson MR, Anagnostopoulos I, Lamping M, Gonzalez-Barca E, Climent F, Salar A, Castellvi J, Abrisqueta P, Menarguez J, Aldamiz T, Richter J, Klapper W, Tzankov A, Dirnhofer S, Rosenwald A, Mate JL, Tapia G, Lenz P, Miething C, Hartmann W, Chapuy B, Fend F, Ott G, Navarro JT, Grau M, Lenz G. Nat Commun 12: 2021 5183	15

Publications

Citations

Molecular and functional profiling identifies therapeutically targetable vulnerabilities in plasmablastic lymphoma.
Frontzek F, Staiger AM, Zapukhlyak M, Xu W, Bonzheim I, Borgmann V, Sander P, Baptista MJ, Heming JN, Berning P, Wullenkord R, Erdmann T, Lutz M, Veratti P, Ehrenfeld S, Wienand K, Horn H, Goodlad JR, Wilson MR, Anagnostopoulos I, Lamping M, Gonzalez-Barca E, Climent F, Salar A, Castellvi J, Abrisqueta P, Menarguez J, Aldamiz T, Richter J, Klapper W, Tzankov A, Dirnhofer S, Rosenwald A, Mate JL, Tapia G, Lenz P, Miething C, Hartmann W, Chapuy B, Fend F, Ott G, Navarro JT, Grau M, Lenz G. Nat Commun 12: 2021 5183