Detection of tumor-derived DNA in cerebrospinal fluid of patients with primary tumors of the brain and spinal cord

Yuxuan Wang; Simeon Springer; Ming Zhang; K. Wyatt Mcmahon; Isaac Kinde; Lisa Dobbyn; Janine Ptak; Henry Brem; Kaisorn Chaichana; Gary L. Gallia; Ziya L. Gokaslan; Mari L. Groves; George I. Jallo; Michael Lim; Alessandro Olivi; Alfredo Quinones-Hinojosa; Daniele Rigamonti; Greg J. Riggins; Daniel M. Sciubba; Jon D. Weingart; Jean-Paul Wolinsky; Xiaobu Ye; Sueli Mieko Oba-Shinjo; Suely K. N. Marie; Matthias Holdhoff; Nishant Agrawal; Luis A. Diaz; Nickolas Papadopoulos; Kenneth W. Kinzler; Bert Vogelstein; Chetan Bettegowda

doi:10.1073/pnas.1511694112

Detection of tumor-derived DNA in cerebrospinal fluid of patients with primary tumors of the brain and spinal cord

Yuxuan Wang, Simeon Springer, Ming Zhang, K. Wyatt Mcmahon, Isaac Kinde, Lisa Dobbyn, Janine Ptak, Henry Brem, Kaisorn Chaichana, Gary L. Gallia, Ziya L. Gokaslan, Mari L. Groves, George I. Jallo, Michael Lim, Alessandro Olivi, Alfredo Quinones-Hinojosa, Daniele Rigamonti, Greg J. Riggins, Daniel M. Sciubba, Jon D. WeingartJean-Paul Wolinsky, Xiaobu Ye, Sueli Mieko Oba-Shinjo, Suely K. N. Marie, Matthias Holdhoff, Nishant Agrawal, Luis A. Diaz, Nickolas Papadopoulos, Kenneth W. Kinzler, Bert Vogelstein, Chetan Bettegowda

Risultato della ricerca: Contributo in rivista › Articolo in rivista

163 Citazioni (Scopus)

Abstract

Cell-free DNA shed by cancer cells has been shown to be a rich source of putative tumor-specific biomarkers. Because cell-free DNA from brain and spinal cord tumors cannot usually be detected in the blood, we studied whether the cerebrospinal fluid (CSF) that bathes the CNS is enriched for tumor DNA, here termed CSF-tDNA. We analyzed 35 primary CNS malignancies and found at least one mutation in each tumor using targeted or genome-wide sequencing. Using these patient-specific mutations as biomarkers, we identified detectable levels of CSF-tDNA in 74% [95% confidence interval (95% CI) = 57-88%] of cases. All medulloblastomas, ependymomas, and high-grade gliomas that abutted a CSF space were detectable (100% of 21 cases; 95% CI = 88-100%), whereas no CSF-tDNA was detected in patients whose tumors were not directly adjacent to a CSF reservoir (P < 0.0001, Fisher's exact test). These results suggest that CSF-tDNA could be useful for the management of patients with primary tumors of the brain or spinal cord.

Lingua originale	English
pagine (da-a)	9704-9709
Numero di pagine	6
Rivista	Proceedings of the National Academy of Sciences of the United States of America
Volume	112
DOI	https://doi.org/10.1073/pnas.1511694112
Stato di pubblicazione	Pubblicato - 2015

Keywords

Adolescent
Adult
Aged
Aged, 80 and over
Biomarker
Brain Neoplasms
CNS tumors
CSF-tDNA
Child
Child, Preschool
DNA Mutational Analysis
DNA, Neoplasm
Demography
Exons
Female
Genome, Human
Humans
Magnetic Resonance Imaging
Male
Middle Aged
Multivariate Analysis
Mutation
Spinal Cord Neoplasms

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Wang, Y., Springer, S., Zhang, M., Mcmahon, K. W., Kinde, I., Dobbyn, L., Ptak, J., Brem, H., Chaichana, K., Gallia, G. L., Gokaslan, Z. L., Groves, M. L., Jallo, G. I., Lim, M., Olivi, A., Quinones-Hinojosa, A., Rigamonti, D., Riggins, G. J., Sciubba, D. M., ... Bettegowda, C. (2015). Detection of tumor-derived DNA in cerebrospinal fluid of patients with primary tumors of the brain and spinal cord. Proceedings of the National Academy of Sciences of the United States of America, 112, 9704-9709. https://doi.org/10.1073/pnas.1511694112

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title = "Detection of tumor-derived DNA in cerebrospinal fluid of patients with primary tumors of the brain and spinal cord",

abstract = "Cell-free DNA shed by cancer cells has been shown to be a rich source of putative tumor-specific biomarkers. Because cell-free DNA from brain and spinal cord tumors cannot usually be detected in the blood, we studied whether the cerebrospinal fluid (CSF) that bathes the CNS is enriched for tumor DNA, here termed CSF-tDNA. We analyzed 35 primary CNS malignancies and found at least one mutation in each tumor using targeted or genome-wide sequencing. Using these patient-specific mutations as biomarkers, we identified detectable levels of CSF-tDNA in 74% [95% confidence interval (95% CI) = 57-88%] of cases. All medulloblastomas, ependymomas, and high-grade gliomas that abutted a CSF space were detectable (100% of 21 cases; 95% CI = 88-100%), whereas no CSF-tDNA was detected in patients whose tumors were not directly adjacent to a CSF reservoir (P < 0.0001, Fisher's exact test). These results suggest that CSF-tDNA could be useful for the management of patients with primary tumors of the brain or spinal cord.",

keywords = "Adolescent, Adult, Aged, Aged, 80 and over, Biomarker, Brain Neoplasms, CNS tumors, CSF-tDNA, Child, Child, Preschool, DNA Mutational Analysis, DNA, Neoplasm, Demography, Exons, Female, Genome, Human, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Multivariate Analysis, Mutation, Spinal Cord Neoplasms, Adolescent, Adult, Aged, Aged, 80 and over, Biomarker, Brain Neoplasms, CNS tumors, CSF-tDNA, Child, Child, Preschool, DNA Mutational Analysis, DNA, Neoplasm, Demography, Exons, Female, Genome, Human, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Multivariate Analysis, Mutation, Spinal Cord Neoplasms",

author = "Yuxuan Wang and Simeon Springer and Ming Zhang and Mcmahon, {K. Wyatt} and Isaac Kinde and Lisa Dobbyn and Janine Ptak and Henry Brem and Kaisorn Chaichana and Gallia, {Gary L.} and Gokaslan, {Ziya L.} and Groves, {Mari L.} and Jallo, {George I.} and Michael Lim and Alessandro Olivi and Alfredo Quinones-Hinojosa and Daniele Rigamonti and Riggins, {Greg J.} and Sciubba, {Daniel M.} and Weingart, {Jon D.} and Jean-Paul Wolinsky and Xiaobu Ye and Oba-Shinjo, {Sueli Mieko} and Marie, {Suely K. N.} and Matthias Holdhoff and Nishant Agrawal and Diaz, {Luis A.} and Nickolas Papadopoulos and Kinzler, {Kenneth W.} and Bert Vogelstein and Chetan Bettegowda",

year = "2015",

doi = "10.1073/pnas.1511694112",

language = "English",

volume = "112",

pages = "9704--9709",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

issn = "0027-8424",

publisher = "National Academy of Sciences",

}

Wang, Y, Springer, S, Zhang, M, Mcmahon, KW, Kinde, I, Dobbyn, L, Ptak, J, Brem, H, Chaichana, K, Gallia, GL, Gokaslan, ZL, Groves, ML, Jallo, GI, Lim, M, Olivi, A, Quinones-Hinojosa, A, Rigamonti, D, Riggins, GJ, Sciubba, DM, Weingart, JD, Wolinsky, J-P, Ye, X, Oba-Shinjo, SM, Marie, SKN, Holdhoff, M, Agrawal, N, Diaz, LA, Papadopoulos, N, Kinzler, KW, Vogelstein, B & Bettegowda, C 2015, 'Detection of tumor-derived DNA in cerebrospinal fluid of patients with primary tumors of the brain and spinal cord', Proceedings of the National Academy of Sciences of the United States of America, vol. 112, pagg. 9704-9709. https://doi.org/10.1073/pnas.1511694112

TY - JOUR

T1 - Detection of tumor-derived DNA in cerebrospinal fluid of patients with primary tumors of the brain and spinal cord

AU - Wang, Yuxuan

AU - Springer, Simeon

AU - Zhang, Ming

AU - Mcmahon, K. Wyatt

AU - Kinde, Isaac

AU - Dobbyn, Lisa

AU - Ptak, Janine

AU - Brem, Henry

AU - Chaichana, Kaisorn

AU - Gallia, Gary L.

AU - Gokaslan, Ziya L.

AU - Groves, Mari L.

AU - Jallo, George I.

AU - Lim, Michael

AU - Olivi, Alessandro

AU - Quinones-Hinojosa, Alfredo

AU - Rigamonti, Daniele

AU - Riggins, Greg J.

AU - Sciubba, Daniel M.

AU - Weingart, Jon D.

AU - Wolinsky, Jean-Paul

AU - Ye, Xiaobu

AU - Oba-Shinjo, Sueli Mieko

AU - Marie, Suely K. N.

AU - Holdhoff, Matthias

AU - Agrawal, Nishant

AU - Diaz, Luis A.

AU - Papadopoulos, Nickolas

AU - Kinzler, Kenneth W.

AU - Vogelstein, Bert

AU - Bettegowda, Chetan

PY - 2015

Y1 - 2015

N2 - Cell-free DNA shed by cancer cells has been shown to be a rich source of putative tumor-specific biomarkers. Because cell-free DNA from brain and spinal cord tumors cannot usually be detected in the blood, we studied whether the cerebrospinal fluid (CSF) that bathes the CNS is enriched for tumor DNA, here termed CSF-tDNA. We analyzed 35 primary CNS malignancies and found at least one mutation in each tumor using targeted or genome-wide sequencing. Using these patient-specific mutations as biomarkers, we identified detectable levels of CSF-tDNA in 74% [95% confidence interval (95% CI) = 57-88%] of cases. All medulloblastomas, ependymomas, and high-grade gliomas that abutted a CSF space were detectable (100% of 21 cases; 95% CI = 88-100%), whereas no CSF-tDNA was detected in patients whose tumors were not directly adjacent to a CSF reservoir (P < 0.0001, Fisher's exact test). These results suggest that CSF-tDNA could be useful for the management of patients with primary tumors of the brain or spinal cord.

AB - Cell-free DNA shed by cancer cells has been shown to be a rich source of putative tumor-specific biomarkers. Because cell-free DNA from brain and spinal cord tumors cannot usually be detected in the blood, we studied whether the cerebrospinal fluid (CSF) that bathes the CNS is enriched for tumor DNA, here termed CSF-tDNA. We analyzed 35 primary CNS malignancies and found at least one mutation in each tumor using targeted or genome-wide sequencing. Using these patient-specific mutations as biomarkers, we identified detectable levels of CSF-tDNA in 74% [95% confidence interval (95% CI) = 57-88%] of cases. All medulloblastomas, ependymomas, and high-grade gliomas that abutted a CSF space were detectable (100% of 21 cases; 95% CI = 88-100%), whereas no CSF-tDNA was detected in patients whose tumors were not directly adjacent to a CSF reservoir (P < 0.0001, Fisher's exact test). These results suggest that CSF-tDNA could be useful for the management of patients with primary tumors of the brain or spinal cord.

KW - Adolescent

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Biomarker

KW - Brain Neoplasms

KW - CNS tumors

KW - CSF-tDNA

KW - Child

KW - Child, Preschool

KW - DNA Mutational Analysis

KW - DNA, Neoplasm

KW - Demography

KW - Exons

KW - Female

KW - Genome, Human

KW - Humans

KW - Magnetic Resonance Imaging

KW - Male

KW - Middle Aged

KW - Multivariate Analysis

KW - Mutation

KW - Spinal Cord Neoplasms

KW - Adolescent

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Biomarker

KW - Brain Neoplasms

KW - CNS tumors

KW - CSF-tDNA

KW - Child

KW - Child, Preschool

KW - DNA Mutational Analysis

KW - DNA, Neoplasm

KW - Demography

KW - Exons

KW - Female

KW - Genome, Human

KW - Humans

KW - Magnetic Resonance Imaging

KW - Male

KW - Middle Aged

KW - Multivariate Analysis

KW - Mutation

KW - Spinal Cord Neoplasms

UR - http://hdl.handle.net/10807/172361

U2 - 10.1073/pnas.1511694112

DO - 10.1073/pnas.1511694112

M3 - Article

SN - 0027-8424

VL - 112

SP - 9704

EP - 9709

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

ER -

Detection of tumor-derived DNA in cerebrospinal fluid of patients with primary tumors of the brain and spinal cord

Abstract

Keywords

OSS delle Nazioni Unite

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