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

David D W Twa, Fong Chun Chan, Susana Ben-Neriah, Bruce W Woolcock, Anja Mottok, King L Tan, Graham W Slack, Jay Gunawardana, Raymond S Lim, Andrew W McPherson, Robert Kridel, Adele Telenius, David W Scott, Kerry J Savage, Sohrab P Shah, Randy D Gascoyne, Christian Steidl, Blood 123, 2062-5 (2014)
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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.