Frequent mutations in HLA and related genes in extranodal NK/T cell lymphomas. Issue 1 (2nd January 2021)

• Record Type: Journal Article
• Authors: Polprasert, Chantana; Takeuchi, Yasuhide; Makishima, Hideki; Wudhikarn, Kitsada; Kakiuchi, Nobuyuki; Tangnuntachai, Nichthida; Assanasen, Thamathorn; Sitthi, Wimonmas; Muhamad, Hamidah; Lawasut, Panisinee; Kongkiatkamon, Sunisa; Bunworasate, Udomsak; Izutsu, Koji; Shiraishi, Yuichi; Chiba, Kenichi; Tanaka, Hiroko; Miyano, Satoru; Ogawa, Seishi; Yoshida, Kenichi; Rojnuckarin, Ponlapat
• Is Part Of: Leukemia & lymphoma. Volume 62:Issue 1(2021)
• Page Start: 95
• Page End: 103
• Publication Date: 2021-01-02
• Subjects: HLA -- extranodal NK/T cell lymphomas -- Epstein–Barr virus; Leukemia -- Periodicals; Lymphomas -- Periodicals; 616.99419
• DOI: 10.1080/10428194.2020.1821011
• Languages: English
• ISSNs: 1042-8194

Abstract

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.