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Kataoka, Keisuke; Miyoshi, Hiroaki; Sakata, Seiji; Dobashi, Akito; Couronné, Lucile; Kogure, Yasunori; Sato, Yasuharu; Nishida, Kenji; Gion, Yuka; Shiraishi, Yuichi; Tanaka, Hiroko; Chiba, Kenichi; Watatani, Yosaku; Kakiuchi, Nobuyuki; Shiozawa, Yusuke; Yoshizato, Tetsuichi; Yoshida, Kenichi; Makishima, Hideki; Sanada, Masashi; Onozawa, Masahiro; Teshima, Takanori; Yoshiki, Yumiko; Ishida, Tadao; Suzuki, Kenshi; Shimada, Kazuyuki; Tomita, Akihiro; Kato, Motohiro; Ota, Yasunori; Izutsu, Koji; Demachi-Okamura, Ayako; Akatsuka, Yoshiki; Miyano, Satoru; Yoshino, Tadashi; Gaulard, Philippe; Hermine, Olivier; Takeuchi, Kengo; Ohshima, Koichi; Ogawa, Seishi
Leukemia, 07/2019, Volume: 33, Issue: 7Journal Article
Viral infection induces potent cellular immunity and activated intracellular signaling, which may dictate the driver events involved in immune escape and clonal selection of virus-associated cancers, including Epstein-Barr virus (EBV)-positive lymphomas. Here, we thoroughly interrogated PD-L1/PD-L2-involving somatic aberrations in 384 samples from various lymphoma subtypes using high-throughput sequencing, particularly focusing on virus-associated lymphomas. A high frequency of PD-L1/PD-L2-involving genetic aberrations was observed in EBV-positive lymphomas 33 (22%) of 148 cases, including extranodal NK/T-cell lymphoma (ENKTL, 23%), aggressive NK-cell leukemia (57%), systemic EBV-positive T-cell lymphoproliferative disorder (17%) as well as EBV-positive diffuse large B-cell lymphoma (DLBCL, 19%) and peripheral T-cell lymphoma-not otherwise specified (15%). Predominantly causing a truncation of the 3'-untranslated region, these alterations represented the most prevalent somatic lesions in ENKTL. By contrast, the frequency was much lower in EBV-negative lymphomas regardless of histology type 12 (5%) of 236 cases. Besides PD-L1/PD-L2 alterations, EBV-positive DLBCL exhibited a genetic profile distinct from EBV-negative one, characterized by frequent TET2 and DNMT3A mutations and the paucity of CD79B, MYD88, CDKN2A, and FAS alterations. Our findings illustrate unique genetic features of EBV-associated lymphomas, also suggesting a potential role of detecting PD-L1/PD-L2-involving lesions for these lymphomas to be effectively targeted by immune checkpoint blockade.
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