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.
| Original language | English |
|---|---|
| Journal | Leukemia |
| DOIs | |
| Publication status | Accepted/In press - Jan 1 2019 |
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ASJC Scopus subject areas
- Hematology
- Oncology
- Cancer Research
Cite this
Frequent structural variations involving programmed death ligands in Epstein-Barr virus-associated lymphomas. / 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.
In: Leukemia, 01.01.2019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Frequent structural variations involving programmed death ligands in Epstein-Barr virus-associated lymphomas
AU - Kataoka, Keisuke
AU - Miyoshi, Hiroaki
AU - Sakata, Seiji
AU - Dobashi, Akito
AU - Couronné, Lucile
AU - Kogure, Yasunori
AU - Sato, Yasuharu
AU - Nishida, Kenji
AU - Gion, Yuka
AU - Shiraishi, Yuichi
AU - Tanaka, Hiroko
AU - Chiba, Kenichi
AU - Watatani, Yosaku
AU - Kakiuchi, Nobuyuki
AU - Shiozawa, Yusuke
AU - Yoshizato, Tetsuichi
AU - Yoshida, Kenichi
AU - Makishima, Hideki
AU - Sanada, Masashi
AU - Onozawa, Masahiro
AU - Teshima, Takanori
AU - Yoshiki, Yumiko
AU - Ishida, Tadao
AU - Suzuki, Kenshi
AU - Shimada, Kazuyuki
AU - Tomita, Akihiro
AU - Kato, Motohiro
AU - Ota, Yasunori
AU - Izutsu, Koji
AU - Demachi-Okamura, Ayako
AU - Akatsuka, Yoshiki
AU - Miyano, Satoru
AU - Yoshino, Tadashi
AU - Gaulard, Philippe
AU - Hermine, Olivier
AU - Takeuchi, Kengo
AU - Ohshima, Koichi
AU - Ogawa, Seishi
PY - 2019/1/1
Y1 - 2019/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85060671911&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85060671911&partnerID=8YFLogxK
U2 - 10.1038/s41375-019-0380-5
DO - 10.1038/s41375-019-0380-5
M3 - Article
JO - Leukemia
JF - Leukemia
SN - 0887-6924
ER -