Aono Daisuke, Kato Toshiaki, Morisawa Akina, Kimata Sakuya, Konishi Seigo, Kometani Mitsuhiro, Yoneda Takashi, Hosomichi Kazuyoshi, Karashima Shigehiro
Department of Health Promotion and Medicine of the Future, Graduate School of Medical Sciences, Kanazawa University, Ishikawa 920-8641, Japan.
Laboratory of Computational Genomics, School of Life Science, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan.
Endocr J. 2025 Mar 3;72(3):325-332. doi: 10.1507/endocrj.EJ24-0346. Epub 2024 Nov 30.
Recently, the usefulness of circulating tumor DNA (ctDNA) analysis in various malignancies has been reported. However, reports on ctDNA analysis in adrenocortical carcinoma (ACC) are few. Therefore, this study aimed to examine the detectability of genetic mutations in ctDNA and the association between ctDNA allelic ratio and disease progression in a patient with post-operative recurrence of ACC. A 77-year-old woman presented with a 5.4 cm left adrenal mass, which was clinically diagnosed as subclinical cortisol-producing ACC on close examination. She underwent left adrenalectomy and was diagnosed with stage II (T2N0M0) ACC. Post-operatively, adjuvant chemotherapy with mitotane was commenced because of histologically high-grade ACC. However, 17 months post-operatively, she had a local recurrence at the left adrenalectomy site. FoundationOne CDx Cancer Genome Profile showed CTNNB1 G34A mutation in the resected adrenal tumor. She had heart failure and interstitial pneumonia and was treated with radiotherapy for local recurrence. Subsequently, lung and liver metastasis appeared post-operatively at 21 and 23 months, respectively. Serum dehydroepiandrosterone sulfate and computed tomography findings at 27 months post-operatively showed disease progression. We collected the peripheral blood at 23 and 27 months post-operatively and analyzed 18 genes associated with adrenal disease in plasma cell-free DNA and the resected adrenal tumor using a next-generation sequencer. At both time-points, CTNNB1 mutations consistent with the primary tumor were observed in ctDNA, with the allelic ratio increasing over time from 8% to 27%. In conclusion, monitoring the ctDNA allelic ratio may be useful for evaluating disease progression in advanced ACC.
最近，已有报道称循环肿瘤DNA（ctDNA）分析在各种恶性肿瘤中具有实用性。然而，关于肾上腺皮质癌（ACC）的ctDNA分析报告却很少。因此，本研究旨在检测一名ACC术后复发患者ctDNA中基因突变的可检测性以及ctDNA等位基因比率与疾病进展之间的关联。一名77岁女性出现一个5.4厘米的左肾上腺肿块，经仔细检查临床诊断为亚临床皮质醇分泌型ACC。她接受了左肾上腺切除术，并被诊断为II期（T2N0M0）ACC。术后，由于组织学上为高级别ACC，开始使用米托坦进行辅助化疗。然而，术后17个月，她在左肾上腺切除部位出现局部复发。FoundationOne CDx癌症基因组图谱显示切除的肾上腺肿瘤中存在CTNNB1 G34A突变。她患有心力衰竭和间质性肺炎，并接受了局部复发的放射治疗。随后，术后分别在21个月和23个月出现肺和肝转移。术后27个月时血清硫酸脱氢表雄酮和计算机断层扫描结果显示疾病进展。我们在术后23个月和27个月采集外周血，使用下一代测序仪分析了血浆游离DNA和切除的肾上腺肿瘤中与肾上腺疾病相关的18个基因。在两个时间点，ctDNA中均观察到与原发肿瘤一致的CTNNB1突变，等位基因比率随时间从8%增加到27%。总之,监测ctDNA等位基因比率可能有助于评估晚期ACC中的疾病进展。
