論文 - 詳細
| RRC ID | 54835 |
|---|---|
| 著者 | Kataoka K, Miyoshi H, Sakata S, Dobashi A, Couronné L, Kogure Y, Sato Y, Nishida K, Gion Y, Shiraishi Y, Tanaka H, Chiba K, Watatani Y, Kakiuchi N, Shiozawa Y, Yoshizato T, Yoshida K, Makishima H, Sanada M, Onozawa M, Teshima T, Yoshiki Y, Ishida T, Suzuki K, Shimada K, Tomita A, Kato M, Ota Y, Izutsu K, Demachi-Okamura A, Akatsuka Y, Miyano S, Yoshino T, Gaulard P, Hermine O, Takeuchi K, Ohshima K, Ogawa S. |
| タイトル | Frequent structural variations involving programmed death ligands in Epstein-Barr virus-associated lymphomas. |
| ジャーナル | Leukemia |
| 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. |
| 巻・号 | 33(7) |
| ページ | 1687-1699 |
| 公開日 | 2019-7-1 |
| DOI | 10.1038/s41375-019-0380-5 |
| PII | 10.1038/s41375-019-0380-5 |
| PMID | 30683910 |
| PMC | PMC6755969 |
| MeSH | B7-H1 Antigen / genetics* Biomarkers, Tumor / genetics* Epstein-Barr Virus Infections / complications* Epstein-Barr Virus Infections / virology Gene Expression Regulation, Neoplastic Genetic Variation* Herpesvirus 4, Human / isolation & purification Humans Ligands Lymphoma, Extranodal NK-T-Cell / genetics* Lymphoma, Extranodal NK-T-Cell / immunology Lymphoma, Extranodal NK-T-Cell / virology Lymphoma, Large B-Cell, Diffuse / genetics* Lymphoma, Large B-Cell, Diffuse / immunology Lymphoma, Large B-Cell, Diffuse / virology Lymphoma, T-Cell, Peripheral / genetics* Lymphoma, T-Cell, Peripheral / immunology Lymphoma, T-Cell, Peripheral / virology Programmed Cell Death 1 Ligand 2 Protein / genetics* |
| IF | 9.944 |
| 引用数 | 12 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | 293T(RCB2202) |