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Frequent structural variations involving programmed death ligands in Epstein-Barr virus-associated lymphomas.


ABSTRACT: 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.

SUBMITTER: Kataoka K 

PROVIDER: S-EPMC6755969 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Frequent structural variations involving programmed death ligands in Epstein-Barr virus-associated lymphomas.

Kataoka Keisuke K   Miyoshi Hiroaki H   Sakata Seiji S   Dobashi Akito A   Couronné Lucile L   Kogure Yasunori Y   Sato Yasuharu Y   Nishida Kenji K   Gion Yuka Y   Shiraishi Yuichi Y   Tanaka Hiroko H   Chiba Kenichi K   Watatani Yosaku Y   Kakiuchi Nobuyuki N   Shiozawa Yusuke Y   Yoshizato Tetsuichi T   Yoshida Kenichi K   Makishima Hideki H   Sanada Masashi M   Onozawa Masahiro M   Teshima Takanori T   Yoshiki Yumiko Y   Ishida Tadao T   Suzuki Kenshi K   Shimada Kazuyuki K   Tomita Akihiro A   Kato Motohiro M   Ota Yasunori Y   Izutsu Koji K   Demachi-Okamura Ayako A   Akatsuka Yoshiki Y   Miyano Satoru S   Yoshino Tadashi T   Gaulard Philippe P   Hermine Olivier O   Takeuchi Kengo K   Ohshima Koichi K   Ogawa Seishi S  

Leukemia 20190125 7


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-invol  ...[more]

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