Division of Endocrinology, Department of Internal Medicine, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam 3000 CA, The Netherlands.
Department of Pathology, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam 3000 CA, The Netherlands.
J Clin Endocrinol Metab. 2017 Oct 1;102(10):3611-3615. doi: 10.1210/jc.2017-00174.
The disease course of adrenocortical carcinoma (ACC) patients is heterogeneous. A marker for prognosis and treatment response would facilitate choices for diagnosis and therapy. In other cancer types, circulating cell-free tumor DNA predicted tumor dynamics.
The present pilot study included six patients. Next-generation sequencing (NGS) showed mutations in three ACC cases. From these patients, blood was drawn before (1 to 2 weeks) and after surgery and cell-free circulating DNA (cfDNA) was isolated. Tumor-specific mutations were found in the cfDNA of one of the three patients, with metastasized ACC at diagnosis. NGS of the tumor showed an NRAS mutation (c.182A>G:p.Q61R) in 78%, a TP53 mutation (c.856G>A:p.E286K) in 60%, and a TERT gene mutation (1295250C>T) in 28% of the reads. The preoperative cfDNA showed the same mutations at a frequency of 64%, 32%, and 2%, respectively. The postoperative cfDNA showed the same mutations but at lower frequencies (52%, 16%, and 3%, respectively). The patient was postoperatively treated with mitotane and chemotherapy. No mutations were detected in the corresponding leukocyte DNA or in the cfDNA from the two other patients.
To the best of our knowledge, we report for the first time mutations occurring at high levels in cfDNA collected before and after surgery from one of three patients, after previous identification in the tumor. However, in the cfDNA from two patients with known mutations, we were unable to reliably detect mutations in the cfDNA. Our results indicate that mutation detection in cfDNA can vary among ACC patients, and other approaches might be required to detect the tumor response and monitor progressive disease.
肾上腺皮质癌（ACC）患者的疾病进程具有异质性。一个用于预后和治疗反应的标志物将有助于诊断和治疗选择。在其他癌症类型中，循环无细胞肿瘤 DNA 可预测肿瘤动态。
本初步研究纳入了 6 名患者。下一代测序（NGS）显示 3 例 ACC 病例存在突变。从这些患者中，在术前（1 至 2 周）和术后采集血液并分离无细胞循环 DNA（cfDNA）。在诊断时发生转移的 ACC 的 3 名患者之一的 cfDNA 中发现了肿瘤特异性突变。肿瘤的 NGS 显示 NRAS 突变（c.182A>G：p.Q61R）占 78%，TP53 突变（c.856G>A：p.E286K）占 60%，TERT 基因突变（1295250C>T）占 28%。术前 cfDNA 的突变频率分别为 64%、32%和 2%。术后 cfDNA 显示相同的突变，但频率较低（分别为 52%、16%和 3%）。该患者术后接受米托坦和化疗治疗。在相应的白细胞 DNA 或另外 2 名患者的 cfDNA 中均未检测到突变。
据我们所知，我们首次报道了在术前和术后从 3 名患者中的 1 名患者的 cfDNA 中检测到高频率的突变，而在肿瘤中先前已鉴定出这些突变。然而，在 cfDNA 来自另外两名已知存在突变的患者中，我们无法可靠地检测到 cfDNA 中的突变。我们的结果表明，cfDNA 中的突变检测在 ACC 患者中可能存在差异，可能需要其他方法来检测肿瘤反应并监测进行性疾病。
