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Conference Paper: Early Detection of Medulloblastoma Relapse by Genomic Profiling of CSF-Derived Circulating Tumor DNA

TitleEarly Detection of Medulloblastoma Relapse by Genomic Profiling of CSF-Derived Circulating Tumor DNA
Authors
Issue Date2020
PublisherAmerican Association of Neurological Surgeons. The Journal's web site is located at http://www.thejns-net.org
Citation
2020 American Association of Neurological Surgeons (AANS) 88th Annual Scientific Meeting, Boston, USA, 25-29 April 2020. Oral Presentations from the 2020 AANS Annual Scientific Meeting in Journal of Neurosurgery, 2020, v. 132 n. 4, abstract no. 202 How to Cite?
AbstractIntroduction: Medulloblastoma progression or recurrence occurs in 30% of patients and confers dismal prognosis. Despite incremental advances in multi-modal management and identification of relevant molecular subgroups, suboptimal outcomes in MB is partly due to the lack of sensitive biomarkers for relapse detection and response-adapted treatment personalization. Cell-free circulating tumor DNA (cf/ctDNA) has emerged as a robust platform for tumor detection and characterization through liquid biopsy of the cerebrospinal fluid (CSF). Methods: CSF from MB patients was collected by lumbar puncture prior to therapy, during therapy, and at 3-month interval follow-up as part of institutional clinical trials. cfDNA was isolated and quantified for yield and fragment size from approximately 1 mL of frozen CSF. After construction of next-generation sequencing libraries, low-pass whole-genome sequencing enabled detection of genome-wide chromosomal and focal copy number alterations (CNAs). CNAs detected in cfDNA were compared against known somatic changes in corresponding tumor-tissue. Detectability of tumor-specific CNAs in cfDNA was then correlated with tumor burden, disease course, and patient outcome. Results: In preliminary analysis, tumor-specific CNAs were identified in at least one post-resection timepoint in 22/23 (96%) relapsing patients. Of patients with CSF available at or 3 months prior to clinicoradiographic progression, tumor-specific CNAs were identifiable in 16/17 (94%). Presence of tumor-specific CNAs at the end of therapy alone predicted future relapse in 8/12 (67%). A subset of genomic alterations were divergent from tissue-derived primary tumor profiles, suggesting potential tumor evolution and oncogenic mechanisms underlying treatment failure and relapse. Conclusion: The feasibility and applicability of CSF liquid biopsy for detection and characterization of tumor-derived cfDNA in MB patients is established. With continued expansion of the clinical cohort, we anticipate the broad applicability of CSF-derived cfDNA as an adjunct to clinicoradiographic surveillance while enabling response-adapted treatment.
DescriptionOral Presentation- no. 202
James T. Rutka Pediatric Brain Tumor Award
2020 88th AANS Annual Scientific Meeting was cancelled due to COVID-19
Persistent Identifierhttp://hdl.handle.net/10722/288273
ISSN
2019 Impact Factor: 3.968
2015 SCImago Journal Rankings: 1.673

 

DC FieldValueLanguage
dc.contributor.authorKumar, R-
dc.contributor.authorLiu, APY-
dc.contributor.authorSmith, K-
dc.contributor.authorPaul, L-
dc.contributor.authorGajjar, A-
dc.contributor.authorRobinson, G-
dc.contributor.authorNorthcot, P-
dc.date.accessioned2020-10-05T12:10:27Z-
dc.date.available2020-10-05T12:10:27Z-
dc.date.issued2020-
dc.identifier.citation2020 American Association of Neurological Surgeons (AANS) 88th Annual Scientific Meeting, Boston, USA, 25-29 April 2020. Oral Presentations from the 2020 AANS Annual Scientific Meeting in Journal of Neurosurgery, 2020, v. 132 n. 4, abstract no. 202-
dc.identifier.issn0022-3085-
dc.identifier.urihttp://hdl.handle.net/10722/288273-
dc.descriptionOral Presentation- no. 202-
dc.descriptionJames T. Rutka Pediatric Brain Tumor Award-
dc.description2020 88th AANS Annual Scientific Meeting was cancelled due to COVID-19-
dc.description.abstractIntroduction: Medulloblastoma progression or recurrence occurs in 30% of patients and confers dismal prognosis. Despite incremental advances in multi-modal management and identification of relevant molecular subgroups, suboptimal outcomes in MB is partly due to the lack of sensitive biomarkers for relapse detection and response-adapted treatment personalization. Cell-free circulating tumor DNA (cf/ctDNA) has emerged as a robust platform for tumor detection and characterization through liquid biopsy of the cerebrospinal fluid (CSF). Methods: CSF from MB patients was collected by lumbar puncture prior to therapy, during therapy, and at 3-month interval follow-up as part of institutional clinical trials. cfDNA was isolated and quantified for yield and fragment size from approximately 1 mL of frozen CSF. After construction of next-generation sequencing libraries, low-pass whole-genome sequencing enabled detection of genome-wide chromosomal and focal copy number alterations (CNAs). CNAs detected in cfDNA were compared against known somatic changes in corresponding tumor-tissue. Detectability of tumor-specific CNAs in cfDNA was then correlated with tumor burden, disease course, and patient outcome. Results: In preliminary analysis, tumor-specific CNAs were identified in at least one post-resection timepoint in 22/23 (96%) relapsing patients. Of patients with CSF available at or 3 months prior to clinicoradiographic progression, tumor-specific CNAs were identifiable in 16/17 (94%). Presence of tumor-specific CNAs at the end of therapy alone predicted future relapse in 8/12 (67%). A subset of genomic alterations were divergent from tissue-derived primary tumor profiles, suggesting potential tumor evolution and oncogenic mechanisms underlying treatment failure and relapse. Conclusion: The feasibility and applicability of CSF liquid biopsy for detection and characterization of tumor-derived cfDNA in MB patients is established. With continued expansion of the clinical cohort, we anticipate the broad applicability of CSF-derived cfDNA as an adjunct to clinicoradiographic surveillance while enabling response-adapted treatment.-
dc.languageeng-
dc.publisherAmerican Association of Neurological Surgeons. The Journal's web site is located at http://www.thejns-net.org-
dc.relation.ispartofJournal of Neurosurgery-
dc.relation.ispartof2020 American Association of Neurological Surgeons (AANS) 88th Annual Scientific Meeting (Cancelled)-
dc.titleEarly Detection of Medulloblastoma Relapse by Genomic Profiling of CSF-Derived Circulating Tumor DNA-
dc.typeConference_Paper-
dc.identifier.emailLiu, APY: apyliu@hku.hk-
dc.identifier.authorityLiu, APY=rp01357-
dc.description.natureabstract-
dc.identifier.hkuros315005-
dc.identifier.volume132-
dc.identifier.issue4-
dc.publisher.placeUnited States-
dc.identifier.partofdoi10.3171/2020.4.JNS.AANS2020abstracts-

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