Medical Oncology Session No.1, Cancer Hospital of Shantou University Medical College, Shantou, China.
Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, China.
Ann Hematol. 2024 Oct;103(10):4135-4144. doi: 10.1007/s00277-024-05782-0. Epub 2024 Jul 16.
Lymphoma tissue biopsies cannot fully capture genetic features due to accessibility and heterogeneity. We aimed to assess the applicability of circulating tumor DNA (ctDNA) for genomic profiling and disease surveillance in classic Hodgkin lymphoma (cHL), primary mediastinal large B-cell lymphoma (PMBCL), and diffuse large B-cell lymphoma (DLBCL).
Tumor tissue and/or liquid biopsies of 49 cHLs, 32 PMBCLs, and 74 DLBCLs were subject to next-generation sequencing targeting 475 genes. The concordance of genetic aberrations in ctDNA and paired tissues was investigated, followed by elevating ctDNA-based mutational landscapes and the correlation between ctDNA dynamics and radiological response/progression.
ctDNA exhibited high concordance with tissue samples in cHL (78%), PMBCL (84%), and DLBCL (78%). In cHL, more unique mutations were detected in ctDNA than in tissue biopsies (P < 0.01), with higher variant allele frequencies (P < 0.01). Distinct genomic features in cHL, PMBCL, and DLBCL, including STAT6, SOCS1, BTG2, and PIM1 alterations, could be captured by ctDNA alone. Prevalent PD-L1/PD-L2 amplifications were associated with more concomitant alterations in PMBCL (P < 0.01). Moreover, ctDNA fluctuation could reflect treatment responses and indicate relapse before imaging diagnosis.
Lymphoma genomic profiling by ctDNA was concordant with that by tumor tissues. ctDNA might also be applied in lymphoma surveillance.
由于可及性和异质性，淋巴瘤组织活检无法完全捕获遗传特征。我们旨在评估循环肿瘤 DNA（ctDNA）在经典霍奇金淋巴瘤（cHL）、原发性纵隔大 B 细胞淋巴瘤（PMBCL）和弥漫性大 B 细胞淋巴瘤（DLBCL）中的基因组分析和疾病监测中的适用性。
对 49 例 cHL、32 例 PMBCL 和 74 例 DLBCL 的肿瘤组织和/或液体活检进行了靶向 475 个基因的下一代测序。研究了 ctDNA 与配对组织中遗传异常的一致性，随后提高了基于 ctDNA 的突变景观以及 ctDNA 动态与放射学反应/进展之间的相关性。
ctDNA 在 cHL（78%）、PMBCL（84%）和 DLBCL（78%）中与组织样本具有高度一致性。在 cHL 中，ctDNA 中检测到的独特突变比组织活检更多（P<0.01），且变异等位基因频率更高（P<0.01）。cHL、PMBCL 和 DLBCL 中独特的基因组特征，包括 STAT6、SOCS1、BTG2 和 PIM1 改变，仅通过 ctDNA 即可捕获。普遍存在的 PD-L1/PD-L2 扩增与 PMBCL 中更多的伴随改变相关（P<0.01）。此外，ctDNA 的波动可以反映治疗反应，并在影像学诊断之前提示复发。
ctDNA 对淋巴瘤基因组分析与肿瘤组织分析一致。ctDNA 也可能应用于淋巴瘤监测。
