Department of Laboratory Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Korea.
Department of Pathology, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Korea.
Cancer Res Treat. 2024 Jan;56(1):314-323. doi: 10.4143/crt.2023.667. Epub 2023 Jul 17.
We designed and evaluated the clinical performance of a plasma circulating tumor DNA (ctDNA) panel of 112 genes in various subtypes of lymphoma.
Targeted deep sequencing with an error-corrected algorithm was performed in ctDNA from plasma samples that were collected before treatment in 42 lymphoma patients. Blood buffy coat was utilized as a germline control. We evaluated the targeted gene panel using mutation detection concordance on the plasma samples with matched tissue samples analyzed the mutation profiles of the ctDNA.
Next-generation sequencing analysis using matched tissue samples was available for 18 of the 42 patients. At least one mutation was detected in the majority of matched tissue biopsy samples (88.9%) and plasma samples (83.3%). A considerable number of mutations (40.4%) that were detected in the tissue samples were also found in the matched plasma samples. Majority of patients (21/42) were diffuse large B cell lymphoma patients. The overall detection rate of ctDNA in patients was 85.7% (36/42). The frequently mutated genes included PIM1, TET2, BCL2, KMT2D, KLHL6, HIST1H1E, and IRF8. A cutoff concentration (4,506 pg/mL) of ctDNA provided 88.9% sensitivity and 82.1% specificity to predict ctDNA mutation detection. The ctDNA concentration correlated with elevated lactate dehydrogenase level and the disease stage.
Our design panel can detect many actionable gene mutations, including those at low frequency. Therefore, liquid biopsy can be applied clinically in the evaluation of lymphoma patients, especially in aggressive lymphoma patients.
我们设计并评估了针对各种淋巴瘤亚型的 112 个基因的血浆循环肿瘤 DNA（ctDNA）面板的临床性能。
对 42 名淋巴瘤患者治疗前采集的血浆样本中的 ctDNA 进行靶向深度测序，采用纠错算法。利用血液白细胞层作为种系对照。我们评估了利用与经匹配的组织样本进行一致性检测的靶向基因面板，分析了 ctDNA 的突变特征。
42 名患者中有 18 名可获得匹配的组织样本进行下一代测序分析。大多数匹配的组织活检样本（88.9%）和血浆样本（83.3%）中均检测到至少一种突变。在组织样本中检测到的大量突变（40.4%）也在匹配的血浆样本中发现。大多数患者（21/42）为弥漫性大 B 细胞淋巴瘤患者。总体上，ctDNA 在患者中的检测率为 85.7%（36/42）。常见的突变基因包括 PIM1、TET2、BCL2、KMT2D、KLHL6、HIST1H1E 和 IRF8。ctDNA 的截断浓度（4,506pg/mL）可提供 88.9%的敏感性和 82.1%的特异性来预测 ctDNA 突变检测。ctDNA 浓度与乳酸脱氢酶水平升高和疾病分期相关。
我们的设计面板可以检测到许多可操作的基因突变，包括低频突变。因此，液体活检可在评估淋巴瘤患者，特别是侵袭性淋巴瘤患者中得到临床应用。
