Lee Jiyeon, Yoon Sang Eun, Kim Seok Jin, Kim Won Seog, Cho Junhun
Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, #81, Irown-ro, Gangnam-gu, Seoul, 06351, Korea.
Division of Hematology and Oncology, Department of Internal Medicine, Sungkyunkwan University School of Medicine, Seoul, Korea.
Ann Hematol. 2024 Dec;103(12):5749-5757. doi: 10.1007/s00277-024-06035-w. Epub 2024 Nov 26.
Extranodal NK/T-cell lymphoma (ENKTL) is a malignant lymphoma that is associated with Epstein-Barr virus (EBV) infection and poor prognosis. Several clinical risk stratification tools for ENKTL patients have been developed; however, their relationship with molecular alterations of tumor is unclear. We performed panel-based next generation sequencing (NGS) on formalin-fixed paraffin-embedded tissue of 40 ENKTL patients and analyzed them with the clinicopathological features. Patients with over 60 years of age, non-nasal type, stage III-IV, and distant lymph node involvement were 14 (35.0%), 11 (27.5%), 13 (32.5%), and 11 (27.5%), respectively. EBV DNA was detected in the blood of 30 patients (75.0%). In the NGS analysis, mutations involving the JAK/STAT pathway were the most common (n = 17, 42.5%), followed by epigenetic modifier (n = 12, 30.3%), NF-κB pathway (n = 11, 27.5%), tumor suppressor (n = 10, 25.5%), and RAS/MAPK pathway (n = 9, 22.5%). Among these, alterations involving tumor suppressor (P = 0.022) and RAS/MAPK pathway (P = 0.008) were statistically significant poor prognostic factors. Tumor suppressor gene mutations were statistically significantly related to stage III-IV (P = 0.006), distant lymph node involvement (P = 0.002), and prognostic index for natural killer cell lymphoma-EBV (PINK-E) high risk group (P = 0.017). However, alterations involving RAS/MAPK pathway did not significantly correlated with PINK-E or its components. Alterations involving tumor suppressor genes and RAS/MAPK pathway are associated with poor prognosis in ENKTL patients. Tumor suppressor gene mutations are generally correlated with previously known risk factors; however, RAS/MAPK pathway alterations are not.
结外NK/T细胞淋巴瘤（ENKTL）是一种与EB病毒（EBV）感染相关且预后较差的恶性淋巴瘤。目前已开发出几种针对ENKTL患者的临床风险分层工具；然而，它们与肿瘤分子改变之间的关系尚不清楚。我们对40例ENKTL患者的福尔马林固定石蜡包埋组织进行了基于 panel 的二代测序（NGS），并结合临床病理特征进行分析。年龄超过60岁、非鼻型、Ⅲ - Ⅳ期及有远处淋巴结受累的患者分别有14例（35.0%）、11例（27.5%）、13例（32.5%）和11例（27.5%）。30例患者（75.0%）血液中检测到EBV DNA。在NGS分析中，涉及JAK/STAT通路的突变最为常见（n = 17，42.5%），其次是表观遗传修饰因子（n = 12，30.3%）、NF - κB通路（n = 11，27.5%）、肿瘤抑制基因（n = 10，25.5%）和RAS/MAPK通路（n = 9，22.5%）。其中，涉及肿瘤抑制基因（P = 0.022）和RAS/MAPK通路（P = 0.008）的改变是具有统计学意义的不良预后因素。肿瘤抑制基因突变与Ⅲ - Ⅳ期（P = 0.006）、远处淋巴结受累（P = 0.002）以及自然杀伤细胞淋巴瘤 - EBV预后指数（PINK - E）高危组（P = 0.017）具有统计学意义的相关性。然而，涉及RAS/MAPK通路的改变与PINK - E或其组成部分无显著相关性。涉及肿瘤抑制基因和RAS/MAPK通路的改变与ENKTL患者的不良预后相关。肿瘤抑制基因突变通常与先前已知的风险因素相关；然而，RAS/MAPK通路改变并非如此。
