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

TitleSerial assessment of measurable residual disease in medulloblastoma liquid biopsies
Authors
Keywordschildhood cancer
medulloblastoma
liquid biopsy
cell-free DNA
measurable residual disease
Issue Date2021
PublisherCell Press. The Journal's web site is located at http://www.elsevier.com/locate/ccell
Citation
Cancer Cell, 2021, v. 39 n. 11, p. 1519-1530.e4 How to Cite?
AbstractNearly 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. © 2021
Persistent Identifierhttp://hdl.handle.net/10722/308523
ISSN
2023 Impact Factor: 48.8
2023 SCImago Journal Rankings: 17.507
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLiu, APY-
dc.contributor.authorSmith, KS-
dc.contributor.authorKumar, R-
dc.contributor.authorPaul, L-
dc.contributor.authorBihannic, L-
dc.contributor.authorLin, T-
dc.contributor.authorMaass, KK-
dc.contributor.authorPajtler, KW-
dc.contributor.authorChintagumpala, M-
dc.contributor.authorSu, JM-
dc.contributor.authorBouffet, E-
dc.contributor.authorFisher, MJ-
dc.contributor.authorGururangan, S-
dc.contributor.authorCohn, R-
dc.contributor.authorHassall, T-
dc.contributor.authorHansford, JR-
dc.contributor.authorJr, PK-
dc.contributor.authorBoop, FA-
dc.contributor.authorStewart, CF-
dc.contributor.authorHarreld, JH-
dc.contributor.authorMerchant, TE-
dc.contributor.authorTatevossian, RG-
dc.contributor.authorNeale, G-
dc.contributor.authorLear, M-
dc.contributor.authorKlco, JM-
dc.contributor.authorOrr, BA-
dc.contributor.authorEllison, DW-
dc.contributor.authorGilbertson, RJ-
dc.contributor.authorOnar-Thomas, A-
dc.contributor.authorGajjar, A-
dc.contributor.authorRobinson, GW-
dc.contributor.authorNorthcott, PA-
dc.date.accessioned2021-12-01T07:54:28Z-
dc.date.available2021-12-01T07:54:28Z-
dc.date.issued2021-
dc.identifier.citationCancer Cell, 2021, v. 39 n. 11, p. 1519-1530.e4-
dc.identifier.issn1535-6108-
dc.identifier.urihttp://hdl.handle.net/10722/308523-
dc.description.abstractNearly 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. © 2021-
dc.languageeng-
dc.publisherCell Press. The Journal's web site is located at http://www.elsevier.com/locate/ccell-
dc.relation.ispartofCancer Cell-
dc.subjectchildhood cancer-
dc.subjectmedulloblastoma-
dc.subjectliquid biopsy-
dc.subjectcell-free DNA-
dc.subjectmeasurable residual disease-
dc.titleSerial assessment of measurable residual disease in medulloblastoma liquid biopsies-
dc.typeArticle-
dc.identifier.emailLiu, APY: apyliu@hku.hk-
dc.identifier.authorityLiu, APY=rp01357-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.ccell.2021.09.012-
dc.identifier.pmid34678152-
dc.identifier.scopuseid_2-s2.0-85118479644-
dc.identifier.hkuros330645-
dc.identifier.volume39-
dc.identifier.issue11-
dc.identifier.spage1519-
dc.identifier.epage1530.e4-
dc.identifier.isiWOS:000718126600002-
dc.publisher.placeUnited States-

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