| Literature DB >> 32964767 |
Chantana Polprasert1,2, Yasuhide Takeuchi3,4,5, Hideki Makishima3,5, Kitsada Wudhikarn1,2, Nobuyuki Kakiuchi3,5, Nichthida Tangnuntachai6, Thamathorn Assanasen6, Wimonmas Sitthi6, Hamidah Muhamad1, Panisinee Lawasut1,2, Sunisa Kongkiatkamon1,2, Udomsak Bunworasate1,2, Koji Izutsu7, Yuichi Shiraishi8, Kenichi Chiba8, Hiroko Tanaka8, Satoru Miyano8, Seishi Ogawa3,5,9, Kenichi Yoshida3, Ponlapat Rojnuckarin1,2.
Abstract
Extranodal NK/T cell lymphomas (ENKTCLs) are aggressive Epstein-Barr virus-associated T/NK neoplasms that predominantly affect Asians. To explore the causative somatic events, we conducted a comprehensive genetic analysis of 19 ENKTCL patients by whole-genome (N = 2), whole-exome (N = 16), and targeted sequencing (N = 15). Commonly deregulated gene pathways in ENKTCLs included epigenetic modifiers (58%, 11/19) followed by human leukocyte antigens (HLAs) and related genes including HLA-A, B2M, TAP1, CD274, and PDCD1LG2 (32%, 6/19), and JAK-STAT pathway (26%, 5/19). Conspicuously, loss-of-function mutations in HLA-A were recurrently identified in ENKTCLs (16%, 3/19). HLA protein expression was examined by immunohistochemistry in 16 patients and lower expression was associated with advanced stages at presentation (p = .007). In conclusion, the defective antigen presenting pathway is common and related to disease progression, suggesting immune escape as a pathogenic mechanism of ENKTCLs.Entities:
Keywords: Epstein–Barr virus; HLA; extranodal NK/T cell lymphomas
Mesh：
Year: 2020 PMID： 32964767 DOI： 10.1080/10428194.2020.1821011
Source DB: PubMed Journal: Leuk Lymphoma ISSN： 1026-8022