Mattox Austin K, Yang Beibei, Douville Christopher, Lo Sheng-Fu, Sciubba Daniel, Wolinsky Jean Paul, Gokaslan Ziya L, Robison Jamie, Blair Cherie, Jiao Yuchen, Bettegowda Chetan
Ludwig Center for Cancer Genetics and Therapeutics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
State Key Lab of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Neurooncol Adv. 2020 Dec 8;3(1):vdaa173. doi: 10.1093/noajnl/vdaa173. eCollection 2021 Jan-Dec.
Chordomas are the most common primary spinal column malignancy in the United States. The aim of this study was to determine whether chordomas may be detected by evaluating mutations in circulating tumor DNA (ctDNA).
Thirty-two patients with a biopsy-confirmed diagnosis of chordoma had blood drawn pre-operatively and/or at follow-up appointments. Mutations in the primary tumor were identified by whole exome sequencing and liquid biopsy by ddPCR and/or RACE-Seq was used to detect one or more of these mutations in plasma ctDNA at concurrent or later time points.
At the time of initial blood draw, 87.1% of patients were ctDNA positive (.001). Follow-up blood draws in twenty of the patients suggest that ctDNA levels may reflect the clinical status of the disease. Patients with positive ctDNA levels were more likely to have greater mutant allele frequencies in their primary tumors ( = .004) and undergo radiotherapy ( = .02), and the presence of ctDNA may correlate with response to systemic chemotherapy and/or disease recurrence.
Detection of ctDNA mutations may allow for the detection and monitoring of disease progression for chordomas.
在美国，脊索瘤是最常见的原发性脊柱恶性肿瘤。本研究的目的是确定是否可以通过评估循环肿瘤DNA（ctDNA）中的突变来检测脊索瘤。
32例经活检确诊为脊索瘤的患者在术前和/或随访时采集血液。通过全外显子测序确定原发性肿瘤中的突变，并采用数字PCR（ddPCR）和/或RACE-Seq进行液体活检，以在同期或后续时间点检测血浆ctDNA中的一种或多种这些突变。
在首次采血时，87.1%的患者ctDNA呈阳性（P<.001）。对20例患者的随访采血表明，ctDNA水平可能反映疾病的临床状态。ctDNA水平呈阳性的患者其原发性肿瘤中更可能具有更高的突变等位基因频率（P = .004），并且更可能接受放疗（P = .02），而且ctDNA的存在可能与全身化疗反应和/或疾病复发相关。
检测ctDNA突变可能有助于脊索瘤疾病进展的检测和监测。
