Objective: To investigate the mutational spectrum in young patients with diffuse large B-cell lymphoma (DLBCL) based on next generation sequencing (NGS), and to provide a basis for in-depth understanding of the molecular biological characteristics and accurate prognosis of young DLBCL.
Methods: From March 2009 to March 2021, 68 young DLBCL patients with complete initial diagnosis data from the Department of Hematology, The People's Hospital Xinjiang Uygur Autonomous Region were retrospectively analyzed, and their paraffin-embedded tissues were subjected to targeted sequencing analysis by NGS technology (including 475 Target genes), and the differences in gene mutation profiles and signaling pathways between high-risk patients with aaIPI ≥2 and low-intermediate risk patients with aaIPI <2 were compared.
Results: A total of 44 high-frequency mutation genes were detected in 68 young DLBCL patients. By comparing the high-frequency mutation genes in aaIPI high-risk group and low-intermediate risk group, it was found that CARD11 mutation in aaIPI high-risk group was significantly higher than that in low-intermediate risk group (P =0.002), while MGA mutation (P =0.037) only appeared in the aaIPI high-risk group, and SPEN mutation (P =0.004) only appeared in the aaIPI low-intermediate risk group. The high-frequency mutation genes and clinical indicators of the aaIPI high-risk group were included in the survival analysis, and the results showed that TP53 (P =0.009, P =0.027), POU2AF1 (P =0.003, P =0.006) and CCND3 (P =0.040, P =0.014) genes mutations were associated with worse PFS and OS, while B2M was associated with better PFS (P =0.014) and OS (P =0.013). Multivariate COX regression analysis showed that the TP53, POU2AF1 and CCND3 were independent risk factors for PFS（P ＝0.021，P =0.005，P =0.020） and OS（P ＝0.042，P =0.010，P =0.013）.
Conclusion: The aaIPI staging combination with molecular biology markers is more conducive to accurately judging the prognosis of young DLBCL patients. TP53, POU2AF1 and CCND3 mutations predict worse survival in the patients with the aaIPI high-risk group.
题目: 基于二代测序技术的年轻弥漫大B细胞淋巴瘤患者的基因突变谱和预后分析.
目的: 应用二代测序技术（NGS）检测年轻弥漫大B细胞淋巴瘤(DLBCL)患者的基因突变谱，为深入理解年轻DLBCL的分子生物学特点及精准预后判断提供依据。.
方法: 回顾性分析2009年3月至2021年3月新疆维吾尔自治区人民医院血液病科初诊资料完整的68例年轻DLBCL患者，采用NGS技术对其石蜡包埋组织进行靶向测序分析（包括475个靶基因），并比较aaIPI≥2分的高危患者和aaIPI＜2分的低中危患者基因突变谱和信号通路的差异。.
结果: 68例年轻DLBCL患者中共检测到44个高频突变基因。通过比较aaIPI高危组和低中危组患者高频突变基因结果显示，aaIPI高危组CARD11突变显著高于低中危组（P =0.002），而MGA突变仅出现在aaIPI高危组（P =0.037），SPEN突变仅出现在aaIPI低中危组（P =0.004）。将aaIPI高危组高频突变基因及临床指标纳入生存分析，结果显示，TP53（P =0.009，P =0.027）、POU2AF1（P =0.003，P =0.006）和CCND3（P =0.040，P =0.014）基因突变与较差的PFS和OS相关,而B2M突变与较好的PFS（P =0.014）和OS（P =0.013）相关。多因素COX回归分析结果显示，TP53、POU2AF1和CCND3突变是影响PFS（P ＝0.021，P =0.005，P =0.020）和OS（P ＝0.042，P =0.010，P =0.013）的独立危险因素。.
结论: aaIPI分期与分子生物学标志相结合更有利于精准判断年轻DLBCL患者预后，TP53、POU2AF1和CCND3突变预示着aaIPI高危组DLBCL患者更差的生存。.
Keywords: gene mutation; prognosis; young; diffuse large B-cell lymphoma; next-generation sequencing.