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Genomic rearrangements involving programmed death ligands are recurrent in primary mediastinal large B-cell lymphoma.

Twa D.D., Chan F.C., Ben-Neriah S., Woolcock B.W., Mottok A., Tan K.L., Slack G.W., Gunawardana J., Lim R.S., McPherson A.W., Kridel R., Telenius A., Scott D.W., Savage K.J., Shah S.P., Gascoyne R.D., Steidl C.

The pathogenesis of primary mediastinal large B-cell lymphoma (PMBCL) is incompletely understood. Recently, specific genotypic and phenotypic features have been linked to tumor cell immune escape mechanisms in PMBCL. We studied 571 B-cell lymphomas with a focus on PMBCL. Using fluorescence in situ hybridization here, we report that the programmed death ligand (PDL) locus (9p24.1) is frequently and specifically rearranged in PMBCL (20%) as compared with diffuse large B-cell lymphoma, follicular lymphoma, and Hodgkin lymphoma. Rearrangement was significantly correlated with overexpression of PDL transcripts. Utilizing high-throughput sequencing techniques, we characterized novel translocations and chimeric fusion transcripts involving PDLs at base-pair resolution. Our data suggest that recurrent genomic rearrangement events underlie an immune privilege phenotype in a subset of B-cell lymphomas.

Blood 123:2062-2065(2014) [PubMed] [Europe PMC]

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