Joshua Casan, Fatimah Jalud, Kaitlyn Kew, Ing Soo Tiong, Francesca Watts, Scott A. Williams, Jesse A. Rudd-Schmidt, Satwica Yerneni, Barbara Withers, Piers Blombery, Teresa Sadras
We report a novel in-frame CD274::PDCD1LG2 fusion in primary mediastinal B-cell lymphoma. Functional studies using expression constructs and CRISPR-engineered lymphoma cells confirmed formation of a PD-L1::PD-L2 chimeric protein and marked upregulation of PD-L1 surface expression, consistent with loss of 3′-UTR-mediated repression. These findings expand the genomic landscape of structural mechanisms driving PD-L1 activation and may inform variant interpretation and patient selection for PD-1 blockade in lymphoma.