Wu Xiao-Bo, Hou Shu-Ling, Zhang Qiao-Hua, Jia Ning, Hou Min, Shui Wen
Department of Lymphoma, Cancer Center, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, China.
Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Oncol. 2022 Jul 5;12:901547. doi: 10.3389/fonc.2022.901547. eCollection 2022.
Lymphoma is a heterogeneous group of tumors in terms of morphological subtypes, molecular alterations, and management. However, data on circulating tumor DNA (ctDNA) mutated genes are limited. The purpose of this study was to investigate the features of the ctDNA mutated genes, the prognosis, and the association between the ctDNA mutated genes and the clinical parameters in lymphoma.
Differences in the ctDNA between the mutated genes and the prognosis of 59 patients with Hodgkin's lymphoma (HL) (10.2%), germinal center B-cell-like lymphoma (GCB) (28.8%), nongerminal center B-cell-like lymphoma (non-GCB) (50.8%), and marginal zone lymphoma (MZL) (10.2%) were analyzed by next generation sequencing (NGS) targeting 121 lymphoma-relevant genes.
Genetic alterations were identified in the ctDNA samples with a median of 6 variants per sample. The genetic variation of the ctDNA in the plasma was found to be significantly correlated with the clinical indices in lymphoma. The genetic heterogeneity of different lymphoma subtypes was clearly observed in the ctDNAs from HL, GCB, non-GCB, and MZL, confirming that distinct molecular mechanisms are involved in the pathogenesis of different lymphomas.
Our findings suggest that NGS-based ctDNA mutation analysis reveals genetic heterogeneity across lymphoma subtypes, with potential implications for discovering therapeutic targets, exploring genomic evolution, and developing risk-adaptive therapies.
淋巴瘤在形态学亚型、分子改变和治疗方面是一组异质性肿瘤。然而,关于循环肿瘤DNA(ctDNA)突变基因的数据有限。本研究的目的是调查ctDNA突变基因的特征、预后以及ctDNA突变基因与淋巴瘤临床参数之间的关联。
通过靶向121个淋巴瘤相关基因的二代测序(NGS)分析了59例霍奇金淋巴瘤(HL)(10.2%)、生发中心B细胞样淋巴瘤(GCB)(28.8%)、非生发中心B细胞样淋巴瘤(非GCB)(50.8%)和边缘区淋巴瘤(MZL)(10.2%)患者的ctDNA突变基因差异及预后。
在ctDNA样本中鉴定出基因改变,每个样本中位数有6个变异。发现血浆中ctDNA的基因变异与淋巴瘤的临床指标显著相关。在HL、GCB、非GCB和MZL的ctDNA中清楚地观察到不同淋巴瘤亚型的基因异质性,证实不同淋巴瘤的发病机制涉及不同的分子机制。
我们的研究结果表明,基于NGS的ctDNA突变分析揭示了淋巴瘤亚型间的基因异质性,对发现治疗靶点、探索基因组进化和开发风险适应性治疗具有潜在意义。