系列评估髓母细胞瘤液体活检中的可测量残留病灶(MRD)，这一成果由美国圣裘德儿童研究医院Paul A. Northcott团队经过不懈努力而取得。这一研究成果发表在2021年10月21日出版的国际学术期刊《癌细胞》上。

在本研究中，研究人员探究了影像学和脑脊液(CSF)衍生的无细胞DNA(cfDNA)作为MRD生物标志物的临床效用，这些样本是从参加前瞻性试验的髓母细胞瘤儿童（123名患者，476个样本）收集的系列样本中得到。使用低覆盖率全基因组测序，研究CSF衍生cfDNA中与肿瘤相关拷贝数变异作为MRD替代物。MRD基线分别在85%的转移性和和54%的局部疾病患者中检测到。MRD阳性患者的数量随着治疗而下降，但持续MRD患者的进展风险显著升高。重要的是，在一半复发的患者中，MRD检测先于放射学进展。该研究结果主张在未来髓母细胞瘤试验中对CSF衍生的液体活检进行前瞻性评估。

据介绍，近三分之一患有髓母细胞瘤（一种小脑恶性胚胎肿瘤）的儿童死于该疾病。通过影像学和脑脊液细胞学进行常规反应监测仍然具有挑战性，并且缺乏测量残留疾灶的标志物。

附：英文原文

Title: Serial assessment of measurable residual disease in medulloblastoma liquid biopsies

Author: Anthony P.Y. Liu, Kyle S. Smith, Rahul Kumar, Leena Paul, Laure Bihannic, Tong Lin, Kendra K. Maass, Kristian W. Pajtler, Murali Chintagumpala, Jack M. Su, Eric Bouffet, Michael J. Fisher, Sridharan Gururangan, Richard Cohn, Tim Hassall, Jordan R. Hansford, Paul Klimo, Frederick A. Boop, Clinton F. Stewart, Julie H. Harreld, Thomas E. Merchant, Ruth G. Tatevossian, Geoffrey Neale, Matthew Lear, Jeffery M. Klco, Brent A. Orr, David W. Ellison, Richard J. Gilbertson, Arzu Onar-Thomas, Amar Gajjar, Giles W. Robinson, Paul A. Northcott

Issue&Volume: 2021-10-21

Abstract: Nearly one-third of children with medulloblastoma, a malignant embryonal tumor ofthe cerebellum, succumb to their disease. Conventional response monitoring by imagingand cerebrospinal fluid (CSF) cytology remains challenging, and a marker for measurableresidual disease (MRD) is lacking. Here, we show the clinical utility of CSF-derivedcell-free DNA (cfDNA) as a biomarker of MRD in serial samples collected from childrenwith medulloblastoma (123 patients, 476 samples) enrolled on a prospective trial.Using low-coverage whole-genome sequencing, tumor-associated copy-number variationsin CSF-derived cfDNA are investigated as an MRD surrogate. MRD is detected at baselinein 85% and 54% of patients with metastatic and localized disease, respectively. Thenumber of MRD-positive patients declines with therapy, yet those with persistent MRDhave significantly higher risk of progression. Importantly, MRD detection precedesradiographic progression in half who relapse. Our findings advocate for the prospectiveassessment of CSF-derived liquid biopsies in future trials for medulloblastoma.

DOI: 10.1016/j.ccell.2021.09.012

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(21)00501-8