Exploring genetic alterations in circulating tumor DNA from cerebrospinal fluid of pediatric medulloblastoma

Abstract Medulloblastoma (MB) is the most common type of brain malignancy in children. Molecular profiling has become an important component to select patients for therapeutic approaches, allowing for personalized therapy. In this study, we successfully identified detectable levels of tumor-derived...

Full description

Bibliographic Details
Main Authors: Yanling Sun, Miao Li, Siqi Ren, Yan Liu, Jin Zhang, Shuting Li, Wenchao Gao, Xiaojun Gong, Jingjing Liu, Yuan Wang, Shuxu Du, Liming Sun, Wanshui Wu, Yongji Tian
Format: Article
Language:English
Published: Nature Portfolio 2021-03-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-021-85178-6
_version_ 1818735281089544192
author Yanling Sun
Miao Li
Siqi Ren
Yan Liu
Jin Zhang
Shuting Li
Wenchao Gao
Xiaojun Gong
Jingjing Liu
Yuan Wang
Shuxu Du
Liming Sun
Wanshui Wu
Yongji Tian
author_facet Yanling Sun
Miao Li
Siqi Ren
Yan Liu
Jin Zhang
Shuting Li
Wenchao Gao
Xiaojun Gong
Jingjing Liu
Yuan Wang
Shuxu Du
Liming Sun
Wanshui Wu
Yongji Tian
author_sort Yanling Sun
collection DOAJ
description Abstract Medulloblastoma (MB) is the most common type of brain malignancy in children. Molecular profiling has become an important component to select patients for therapeutic approaches, allowing for personalized therapy. In this study, we successfully identified detectable levels of tumor-derived cell-free DNA (cfDNA) in cerebrospinal fluid (CSF) samples of patients with MB. Furthermore, cfDNA from CSF can interrogate for tumor-associated molecular clues. MB-associated alterations from CSF, tumor, and post-chemotherapy plasma were compared by deep sequencing on next-generation sequencing platform. Shared alterations exist between CSF and matched tumor tissues. More alternations were detected in circulating tumor DNA from CSF than those in genomic DNA from primary tumor. It was feasible to detect MB-associated mutations in plasma of patients treated with chemotherapy. Collectively, CSF supernatant can be used to monitor genomic alterations, as a superior technique as long as tumor-derived cfDNA can be isolated from CSF successfully.
first_indexed 2024-12-18T00:18:45Z
format Article
id doaj.art-67450cab29a44b85b5b48b10b84d70e3
institution Directory Open Access Journal
issn 2045-2322
language English
last_indexed 2024-12-18T00:18:45Z
publishDate 2021-03-01
publisher Nature Portfolio
record_format Article
series Scientific Reports
spelling doaj.art-67450cab29a44b85b5b48b10b84d70e32022-12-21T21:27:24ZengNature PortfolioScientific Reports2045-23222021-03-011111810.1038/s41598-021-85178-6Exploring genetic alterations in circulating tumor DNA from cerebrospinal fluid of pediatric medulloblastomaYanling Sun0Miao Li1Siqi Ren2Yan Liu3Jin Zhang4Shuting Li5Wenchao Gao6Xiaojun Gong7Jingjing Liu8Yuan Wang9Shuxu Du10Liming Sun11Wanshui Wu12Yongji Tian13Department of Pediatrics, Beijing Shijitan Hospital, Capital Medical UniversityDepartment of Pediatrics, Beijing Shijitan Hospital, Capital Medical UniversityDepartment of Pediatrics, Beijing Shijitan Hospital, Capital Medical UniversityDepartment of Pediatrics, Beijing Shijitan Hospital, Capital Medical UniversityDepartment of Pediatrics, Beijing Shijitan Hospital, Capital Medical UniversityDepartment of Pediatrics, Beijing Shijitan Hospital, Capital Medical UniversityDepartment of Pediatrics, Beijing Shijitan Hospital, Capital Medical UniversityDepartment of Pediatrics, Beijing Shijitan Hospital, Capital Medical UniversityDepartment of Pediatrics, Beijing Shijitan Hospital, Capital Medical UniversityDepartment of Pediatrics, Beijing Shijitan Hospital, Capital Medical UniversityDepartment of Pediatrics, Beijing Shijitan Hospital, Capital Medical UniversityDepartment of Pediatrics, Beijing Shijitan Hospital, Capital Medical UniversityDepartment of Pediatrics, Beijing Shijitan Hospital, Capital Medical UniversityDepartment of Pediatric Neurosurgery, Beijing Tiantan Hospital, Capital Medical UniversityAbstract Medulloblastoma (MB) is the most common type of brain malignancy in children. Molecular profiling has become an important component to select patients for therapeutic approaches, allowing for personalized therapy. In this study, we successfully identified detectable levels of tumor-derived cell-free DNA (cfDNA) in cerebrospinal fluid (CSF) samples of patients with MB. Furthermore, cfDNA from CSF can interrogate for tumor-associated molecular clues. MB-associated alterations from CSF, tumor, and post-chemotherapy plasma were compared by deep sequencing on next-generation sequencing platform. Shared alterations exist between CSF and matched tumor tissues. More alternations were detected in circulating tumor DNA from CSF than those in genomic DNA from primary tumor. It was feasible to detect MB-associated mutations in plasma of patients treated with chemotherapy. Collectively, CSF supernatant can be used to monitor genomic alterations, as a superior technique as long as tumor-derived cfDNA can be isolated from CSF successfully.https://doi.org/10.1038/s41598-021-85178-6
spellingShingle Yanling Sun
Miao Li
Siqi Ren
Yan Liu
Jin Zhang
Shuting Li
Wenchao Gao
Xiaojun Gong
Jingjing Liu
Yuan Wang
Shuxu Du
Liming Sun
Wanshui Wu
Yongji Tian
Exploring genetic alterations in circulating tumor DNA from cerebrospinal fluid of pediatric medulloblastoma
Scientific Reports
title Exploring genetic alterations in circulating tumor DNA from cerebrospinal fluid of pediatric medulloblastoma
title_full Exploring genetic alterations in circulating tumor DNA from cerebrospinal fluid of pediatric medulloblastoma
title_fullStr Exploring genetic alterations in circulating tumor DNA from cerebrospinal fluid of pediatric medulloblastoma
title_full_unstemmed Exploring genetic alterations in circulating tumor DNA from cerebrospinal fluid of pediatric medulloblastoma
title_short Exploring genetic alterations in circulating tumor DNA from cerebrospinal fluid of pediatric medulloblastoma
title_sort exploring genetic alterations in circulating tumor dna from cerebrospinal fluid of pediatric medulloblastoma
url https://doi.org/10.1038/s41598-021-85178-6
work_keys_str_mv AT yanlingsun exploringgeneticalterationsincirculatingtumordnafromcerebrospinalfluidofpediatricmedulloblastoma
AT miaoli exploringgeneticalterationsincirculatingtumordnafromcerebrospinalfluidofpediatricmedulloblastoma
AT siqiren exploringgeneticalterationsincirculatingtumordnafromcerebrospinalfluidofpediatricmedulloblastoma
AT yanliu exploringgeneticalterationsincirculatingtumordnafromcerebrospinalfluidofpediatricmedulloblastoma
AT jinzhang exploringgeneticalterationsincirculatingtumordnafromcerebrospinalfluidofpediatricmedulloblastoma
AT shutingli exploringgeneticalterationsincirculatingtumordnafromcerebrospinalfluidofpediatricmedulloblastoma
AT wenchaogao exploringgeneticalterationsincirculatingtumordnafromcerebrospinalfluidofpediatricmedulloblastoma
AT xiaojungong exploringgeneticalterationsincirculatingtumordnafromcerebrospinalfluidofpediatricmedulloblastoma
AT jingjingliu exploringgeneticalterationsincirculatingtumordnafromcerebrospinalfluidofpediatricmedulloblastoma
AT yuanwang exploringgeneticalterationsincirculatingtumordnafromcerebrospinalfluidofpediatricmedulloblastoma
AT shuxudu exploringgeneticalterationsincirculatingtumordnafromcerebrospinalfluidofpediatricmedulloblastoma
AT limingsun exploringgeneticalterationsincirculatingtumordnafromcerebrospinalfluidofpediatricmedulloblastoma
AT wanshuiwu exploringgeneticalterationsincirculatingtumordnafromcerebrospinalfluidofpediatricmedulloblastoma
AT yongjitian exploringgeneticalterationsincirculatingtumordnafromcerebrospinalfluidofpediatricmedulloblastoma