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000177206 0247_ $$2doi$$a10.1016/j.ccell.2021.09.012
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000177206 041__ $$aEnglish
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000177206 1001_ $$aLiu, Anthony P Y$$b0
000177206 245__ $$aSerial assessment of measurable residual disease in medulloblastoma liquid biopsies.
000177206 260__ $$aNew York, NY$$bElsevier$$c2021
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000177206 500__ $$a2021 Nov 8;39(11):1519-1530.e4
000177206 520__ $$aNearly one-third of children with medulloblastoma, a malignant embryonal tumor of the cerebellum, succumb to their disease. Conventional response monitoring by imaging and cerebrospinal fluid (CSF) cytology remains challenging, and a marker for measurable residual disease (MRD) is lacking. Here, we show the clinical utility of CSF-derived cell-free DNA (cfDNA) as a biomarker of MRD in serial samples collected from children with medulloblastoma (123 patients, 476 samples) enrolled on a prospective trial. Using low-coverage whole-genome sequencing, tumor-associated copy-number variations in CSF-derived cfDNA are investigated as an MRD surrogate. MRD is detected at baseline in 85% and 54% of patients with metastatic and localized disease, respectively. The number of MRD-positive patients declines with therapy, yet those with persistent MRD have significantly higher risk of progression. Importantly, MRD detection precedes radiographic progression in half who relapse. Our findings advocate for the prospective assessment of CSF-derived liquid biopsies in future trials for medulloblastoma.
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000177206 650_7 $$2Other$$abiomarkers
000177206 650_7 $$2Other$$acell-free DNA
000177206 650_7 $$2Other$$acerebrospinal fluid
000177206 650_7 $$2Other$$achildhood cancer
000177206 650_7 $$2Other$$aliquid biopsy
000177206 650_7 $$2Other$$ameasurable residual disease
000177206 650_7 $$2Other$$amedulloblastoma
000177206 650_7 $$2Other$$amicroscopic residual disease
000177206 650_7 $$2Other$$aminimal residual disease
000177206 650_7 $$2Other$$arelapse disease
000177206 7001_ $$aSmith, Kyle S$$b1
000177206 7001_ $$aKumar, Rahul$$b2
000177206 7001_ $$aPaul, Leena$$b3
000177206 7001_ $$aBihannic, Laure$$b4
000177206 7001_ $$aLin, Tong$$b5
000177206 7001_ $$0P:(DE-He78)5100059e746b377e2e0a37c0e24f6bf7$$aMaass, Kendra K$$b6$$udkfz
000177206 7001_ $$0P:(DE-He78)a7c1bbac024fa232d9c6b78443328d9d$$aPajtler, Kristian W$$b7$$udkfz
000177206 7001_ $$aChintagumpala, Murali$$b8
000177206 7001_ $$aSu, Jack M$$b9
000177206 7001_ $$aBouffet, Eric$$b10
000177206 7001_ $$aFisher, Michael J$$b11
000177206 7001_ $$aGururangan, Sridharan$$b12
000177206 7001_ $$aCohn, Richard$$b13
000177206 7001_ $$aHassall, Tim$$b14
000177206 7001_ $$aHansford, Jordan R$$b15
000177206 7001_ $$aKlimo, Paul$$b16
000177206 7001_ $$aBoop, Frederick A$$b17
000177206 7001_ $$aStewart, Clinton F$$b18
000177206 7001_ $$aHarreld, Julie H$$b19
000177206 7001_ $$aMerchant, Thomas E$$b20
000177206 7001_ $$aTatevossian, Ruth G$$b21
000177206 7001_ $$aNeale, Geoffrey$$b22
000177206 7001_ $$aLear, Matthew$$b23
000177206 7001_ $$aKlco, Jeffery M$$b24
000177206 7001_ $$aOrr, Brent A$$b25
000177206 7001_ $$aEllison, David W$$b26
000177206 7001_ $$aGilbertson, Richard J$$b27
000177206 7001_ $$aOnar-Thomas, Arzu$$b28
000177206 7001_ $$aGajjar, Amar$$b29
000177206 7001_ $$aRobinson, Giles W$$b30
000177206 7001_ $$aNorthcott, Paul A$$b31
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