title: Evaluating Cancer of the Central Nervous System Through Next-Generation Sequencing of Cerebrospinal Fluid.
abstract: Cancer spread to the central nervous system (CNS) often is diagnosed late and is unresponsive to therapy. Mechanisms of tumor dissemination and evolution within the CNS are largely unknown because of limited access to tumor tissue.
  
  
  
  We sequenced 341 cancer-associated genes in cell-free DNA from cerebrospinal fluid (CSF) obtained through routine lumbar puncture in 53 patients with suspected or known CNS involvement by cancer.
  
  
  
  We detected high-confidence somatic alterations in 63% (20 of 32) of patients with CNS metastases of solid tumors, 50% (six of 12) of patients with primary brain tumors, and 0% (zero of nine) of patients without CNS involvement by cancer. Several patients with tumor progression in the CNS during therapy with inhibitors of oncogenic kinases harbored mutations in the kinase target or kinase bypass pathways. In patients with glioma, the most common malignant primary brain tumor in adults, examination of cell-free DNA uncovered patterns of tumor evolution, including temozolomide-associated mutations.
  
  
  
  The study shows that CSF harbors clinically relevant genomic alterations in patients with CNS cancers and should be considered for liquid biopsies to monitor tumor evolution in the CNS.
authors.affiliation: Elena I. Pentsova, Ronak H. Shah, Jiabin Tang, Adrienne Boire, Daoqi You, Samuel Briggs, Antonio Omuro, Xuling Lin, Martin Fleisher, Christian Grommes, Katherine S. Panageas, Fanli Meng, S. Duygu Selcuklu, Shahiba Ogilvie, Natalie Distefano, Larisa Shagabayeva, Marc Rosenblum, Lisa M. DeAngelis, Agnes Viale, Ingo K. Mellinghoff, and Michael F. Berger, Memorial Sloan Kettering Cancer Center; Ingo K. Mellinghoff, Weill-Cornell Graduate School of Biomedical Sciences; and Michael F. Berger, Weill-Cornell Medical College, New York, NY.
authors.forename: Elena I
authors.initials: EI
authors.lastname: Pentsova
authors.affiliation: Elena I. Pentsova, Ronak H. Shah, Jiabin Tang, Adrienne Boire, Daoqi You, Samuel Briggs, Antonio Omuro, Xuling Lin, Martin Fleisher, Christian Grommes, Katherine S. Panageas, Fanli Meng, S. Duygu Selcuklu, Shahiba Ogilvie, Natalie Distefano, Larisa Shagabayeva, Marc Rosenblum, Lisa M. DeAngelis, Agnes Viale, Ingo K. Mellinghoff, and Michael F. Berger, Memorial Sloan Kettering Cancer Center; Ingo K. Mellinghoff, Weill-Cornell Graduate School of Biomedical Sciences; and Michael F. Berger, Weill-Cornell Medical College, New York, NY.
authors.forename: Ronak H
authors.initials: RH
authors.lastname: Shah
authors.affiliation: Elena I. Pentsova, Ronak H. Shah, Jiabin Tang, Adrienne Boire, Daoqi You, Samuel Briggs, Antonio Omuro, Xuling Lin, Martin Fleisher, Christian Grommes, Katherine S. Panageas, Fanli Meng, S. Duygu Selcuklu, Shahiba Ogilvie, Natalie Distefano, Larisa Shagabayeva, Marc Rosenblum, Lisa M. DeAngelis, Agnes Viale, Ingo K. Mellinghoff, and Michael F. Berger, Memorial Sloan Kettering Cancer Center; Ingo K. Mellinghoff, Weill-Cornell Graduate School of Biomedical Sciences; and Michael F. Berger, Weill-Cornell Medical College, New York, NY.
authors.forename: Jiabin
authors.initials: J
authors.lastname: Tang
authors.affiliation: Elena I. Pentsova, Ronak H. Shah, Jiabin Tang, Adrienne Boire, Daoqi You, Samuel Briggs, Antonio Omuro, Xuling Lin, Martin Fleisher, Christian Grommes, Katherine S. Panageas, Fanli Meng, S. Duygu Selcuklu, Shahiba Ogilvie, Natalie Distefano, Larisa Shagabayeva, Marc Rosenblum, Lisa M. DeAngelis, Agnes Viale, Ingo K. Mellinghoff, and Michael F. Berger, Memorial Sloan Kettering Cancer Center; Ingo K. Mellinghoff, Weill-Cornell Graduate School of Biomedical Sciences; and Michael F. Berger, Weill-Cornell Medical College, New York, NY.
authors.forename: Adrienne
authors.initials: A
authors.lastname: Boire
authors.affiliation: Elena I. Pentsova, Ronak H. Shah, Jiabin Tang, Adrienne Boire, Daoqi You, Samuel Briggs, Antonio Omuro, Xuling Lin, Martin Fleisher, Christian Grommes, Katherine S. Panageas, Fanli Meng, S. Duygu Selcuklu, Shahiba Ogilvie, Natalie Distefano, Larisa Shagabayeva, Marc Rosenblum, Lisa M. DeAngelis, Agnes Viale, Ingo K. Mellinghoff, and Michael F. Berger, Memorial Sloan Kettering Cancer Center; Ingo K. Mellinghoff, Weill-Cornell Graduate School of Biomedical Sciences; and Michael F. Berger, Weill-Cornell Medical College, New York, NY.
authors.forename: Daoqi
authors.initials: D
authors.lastname: You
authors.affiliation: Elena I. Pentsova, Ronak H. Shah, Jiabin Tang, Adrienne Boire, Daoqi You, Samuel Briggs, Antonio Omuro, Xuling Lin, Martin Fleisher, Christian Grommes, Katherine S. Panageas, Fanli Meng, S. Duygu Selcuklu, Shahiba Ogilvie, Natalie Distefano, Larisa Shagabayeva, Marc Rosenblum, Lisa M. DeAngelis, Agnes Viale, Ingo K. Mellinghoff, and Michael F. Berger, Memorial Sloan Kettering Cancer Center; Ingo K. Mellinghoff, Weill-Cornell Graduate School of Biomedical Sciences; and Michael F. Berger, Weill-Cornell Medical College, New York, NY.
authors.forename: Samuel
authors.initials: S
authors.lastname: Briggs
authors.affiliation: Elena I. Pentsova, Ronak H. Shah, Jiabin Tang, Adrienne Boire, Daoqi You, Samuel Briggs, Antonio Omuro, Xuling Lin, Martin Fleisher, Christian Grommes, Katherine S. Panageas, Fanli Meng, S. Duygu Selcuklu, Shahiba Ogilvie, Natalie Distefano, Larisa Shagabayeva, Marc Rosenblum, Lisa M. DeAngelis, Agnes Viale, Ingo K. Mellinghoff, and Michael F. Berger, Memorial Sloan Kettering Cancer Center; Ingo K. Mellinghoff, Weill-Cornell Graduate School of Biomedical Sciences; and Michael F. Berger, Weill-Cornell Medical College, New York, NY.
authors.forename: Antonio
authors.initials: A
authors.lastname: Omuro
authors.affiliation: Elena I. Pentsova, Ronak H. Shah, Jiabin Tang, Adrienne Boire, Daoqi You, Samuel Briggs, Antonio Omuro, Xuling Lin, Martin Fleisher, Christian Grommes, Katherine S. Panageas, Fanli Meng, S. Duygu Selcuklu, Shahiba Ogilvie, Natalie Distefano, Larisa Shagabayeva, Marc Rosenblum, Lisa M. DeAngelis, Agnes Viale, Ingo K. Mellinghoff, and Michael F. Berger, Memorial Sloan Kettering Cancer Center; Ingo K. Mellinghoff, Weill-Cornell Graduate School of Biomedical Sciences; and Michael F. Berger, Weill-Cornell Medical College, New York, NY.
authors.forename: Xuling
authors.initials: X
authors.lastname: Lin
authors.affiliation: Elena I. Pentsova, Ronak H. Shah, Jiabin Tang, Adrienne Boire, Daoqi You, Samuel Briggs, Antonio Omuro, Xuling Lin, Martin Fleisher, Christian Grommes, Katherine S. Panageas, Fanli Meng, S. Duygu Selcuklu, Shahiba Ogilvie, Natalie Distefano, Larisa Shagabayeva, Marc Rosenblum, Lisa M. DeAngelis, Agnes Viale, Ingo K. Mellinghoff, and Michael F. Berger, Memorial Sloan Kettering Cancer Center; Ingo K. Mellinghoff, Weill-Cornell Graduate School of Biomedical Sciences; and Michael F. Berger, Weill-Cornell Medical College, New York, NY.
authors.forename: Martin
authors.initials: M
authors.lastname: Fleisher
authors.affiliation: Elena I. Pentsova, Ronak H. Shah, Jiabin Tang, Adrienne Boire, Daoqi You, Samuel Briggs, Antonio Omuro, Xuling Lin, Martin Fleisher, Christian Grommes, Katherine S. Panageas, Fanli Meng, S. Duygu Selcuklu, Shahiba Ogilvie, Natalie Distefano, Larisa Shagabayeva, Marc Rosenblum, Lisa M. DeAngelis, Agnes Viale, Ingo K. Mellinghoff, and Michael F. Berger, Memorial Sloan Kettering Cancer Center; Ingo K. Mellinghoff, Weill-Cornell Graduate School of Biomedical Sciences; and Michael F. Berger, Weill-Cornell Medical College, New York, NY.
authors.forename: Christian
authors.initials: C
authors.lastname: Grommes
authors.affiliation: Elena I. Pentsova, Ronak H. Shah, Jiabin Tang, Adrienne Boire, Daoqi You, Samuel Briggs, Antonio Omuro, Xuling Lin, Martin Fleisher, Christian Grommes, Katherine S. Panageas, Fanli Meng, S. Duygu Selcuklu, Shahiba Ogilvie, Natalie Distefano, Larisa Shagabayeva, Marc Rosenblum, Lisa M. DeAngelis, Agnes Viale, Ingo K. Mellinghoff, and Michael F. Berger, Memorial Sloan Kettering Cancer Center; Ingo K. Mellinghoff, Weill-Cornell Graduate School of Biomedical Sciences; and Michael F. Berger, Weill-Cornell Medical College, New York, NY.
authors.forename: Katherine S
authors.initials: KS
authors.lastname: Panageas
authors.affiliation: Elena I. Pentsova, Ronak H. Shah, Jiabin Tang, Adrienne Boire, Daoqi You, Samuel Briggs, Antonio Omuro, Xuling Lin, Martin Fleisher, Christian Grommes, Katherine S. Panageas, Fanli Meng, S. Duygu Selcuklu, Shahiba Ogilvie, Natalie Distefano, Larisa Shagabayeva, Marc Rosenblum, Lisa M. DeAngelis, Agnes Viale, Ingo K. Mellinghoff, and Michael F. Berger, Memorial Sloan Kettering Cancer Center; Ingo K. Mellinghoff, Weill-Cornell Graduate School of Biomedical Sciences; and Michael F. Berger, Weill-Cornell Medical College, New York, NY.
authors.forename: Fanli
authors.initials: F
authors.lastname: Meng
authors.affiliation: Elena I. Pentsova, Ronak H. Shah, Jiabin Tang, Adrienne Boire, Daoqi You, Samuel Briggs, Antonio Omuro, Xuling Lin, Martin Fleisher, Christian Grommes, Katherine S. Panageas, Fanli Meng, S. Duygu Selcuklu, Shahiba Ogilvie, Natalie Distefano, Larisa Shagabayeva, Marc Rosenblum, Lisa M. DeAngelis, Agnes Viale, Ingo K. Mellinghoff, and Michael F. Berger, Memorial Sloan Kettering Cancer Center; Ingo K. Mellinghoff, Weill-Cornell Graduate School of Biomedical Sciences; and Michael F. Berger, Weill-Cornell Medical College, New York, NY.
authors.forename: S Duygu
authors.initials: SD
authors.lastname: Selcuklu
authors.affiliation: Elena I. Pentsova, Ronak H. Shah, Jiabin Tang, Adrienne Boire, Daoqi You, Samuel Briggs, Antonio Omuro, Xuling Lin, Martin Fleisher, Christian Grommes, Katherine S. Panageas, Fanli Meng, S. Duygu Selcuklu, Shahiba Ogilvie, Natalie Distefano, Larisa Shagabayeva, Marc Rosenblum, Lisa M. DeAngelis, Agnes Viale, Ingo K. Mellinghoff, and Michael F. Berger, Memorial Sloan Kettering Cancer Center; Ingo K. Mellinghoff, Weill-Cornell Graduate School of Biomedical Sciences; and Michael F. Berger, Weill-Cornell Medical College, New York, NY.
authors.forename: Shahiba
authors.initials: S
authors.lastname: Ogilvie
authors.affiliation: Elena I. Pentsova, Ronak H. Shah, Jiabin Tang, Adrienne Boire, Daoqi You, Samuel Briggs, Antonio Omuro, Xuling Lin, Martin Fleisher, Christian Grommes, Katherine S. Panageas, Fanli Meng, S. Duygu Selcuklu, Shahiba Ogilvie, Natalie Distefano, Larisa Shagabayeva, Marc Rosenblum, Lisa M. DeAngelis, Agnes Viale, Ingo K. Mellinghoff, and Michael F. Berger, Memorial Sloan Kettering Cancer Center; Ingo K. Mellinghoff, Weill-Cornell Graduate School of Biomedical Sciences; and Michael F. Berger, Weill-Cornell Medical College, New York, NY.
authors.forename: Natalie
authors.initials: N
authors.lastname: Distefano
authors.affiliation: Elena I. Pentsova, Ronak H. Shah, Jiabin Tang, Adrienne Boire, Daoqi You, Samuel Briggs, Antonio Omuro, Xuling Lin, Martin Fleisher, Christian Grommes, Katherine S. Panageas, Fanli Meng, S. Duygu Selcuklu, Shahiba Ogilvie, Natalie Distefano, Larisa Shagabayeva, Marc Rosenblum, Lisa M. DeAngelis, Agnes Viale, Ingo K. Mellinghoff, and Michael F. Berger, Memorial Sloan Kettering Cancer Center; Ingo K. Mellinghoff, Weill-Cornell Graduate School of Biomedical Sciences; and Michael F. Berger, Weill-Cornell Medical College, New York, NY.
authors.forename: Larisa
authors.initials: L
authors.lastname: Shagabayeva
authors.affiliation: Elena I. Pentsova, Ronak H. Shah, Jiabin Tang, Adrienne Boire, Daoqi You, Samuel Briggs, Antonio Omuro, Xuling Lin, Martin Fleisher, Christian Grommes, Katherine S. Panageas, Fanli Meng, S. Duygu Selcuklu, Shahiba Ogilvie, Natalie Distefano, Larisa Shagabayeva, Marc Rosenblum, Lisa M. DeAngelis, Agnes Viale, Ingo K. Mellinghoff, and Michael F. Berger, Memorial Sloan Kettering Cancer Center; Ingo K. Mellinghoff, Weill-Cornell Graduate School of Biomedical Sciences; and Michael F. Berger, Weill-Cornell Medical College, New York, NY.
authors.forename: Marc
authors.initials: M
authors.lastname: Rosenblum
authors.affiliation: Elena I. Pentsova, Ronak H. Shah, Jiabin Tang, Adrienne Boire, Daoqi You, Samuel Briggs, Antonio Omuro, Xuling Lin, Martin Fleisher, Christian Grommes, Katherine S. Panageas, Fanli Meng, S. Duygu Selcuklu, Shahiba Ogilvie, Natalie Distefano, Larisa Shagabayeva, Marc Rosenblum, Lisa M. DeAngelis, Agnes Viale, Ingo K. Mellinghoff, and Michael F. Berger, Memorial Sloan Kettering Cancer Center; Ingo K. Mellinghoff, Weill-Cornell Graduate School of Biomedical Sciences; and Michael F. Berger, Weill-Cornell Medical College, New York, NY.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: DeAngelis
authors.affiliation: Elena I. Pentsova, Ronak H. Shah, Jiabin Tang, Adrienne Boire, Daoqi You, Samuel Briggs, Antonio Omuro, Xuling Lin, Martin Fleisher, Christian Grommes, Katherine S. Panageas, Fanli Meng, S. Duygu Selcuklu, Shahiba Ogilvie, Natalie Distefano, Larisa Shagabayeva, Marc Rosenblum, Lisa M. DeAngelis, Agnes Viale, Ingo K. Mellinghoff, and Michael F. Berger, Memorial Sloan Kettering Cancer Center; Ingo K. Mellinghoff, Weill-Cornell Graduate School of Biomedical Sciences; and Michael F. Berger, Weill-Cornell Medical College, New York, NY.
authors.forename: Agnes
authors.initials: A
authors.lastname: Viale
authors.affiliation: Elena I. Pentsova, Ronak H. Shah, Jiabin Tang, Adrienne Boire, Daoqi You, Samuel Briggs, Antonio Omuro, Xuling Lin, Martin Fleisher, Christian Grommes, Katherine S. Panageas, Fanli Meng, S. Duygu Selcuklu, Shahiba Ogilvie, Natalie Distefano, Larisa Shagabayeva, Marc Rosenblum, Lisa M. DeAngelis, Agnes Viale, Ingo K. Mellinghoff, and Michael F. Berger, Memorial Sloan Kettering Cancer Center; Ingo K. Mellinghoff, Weill-Cornell Graduate School of Biomedical Sciences; and Michael F. Berger, Weill-Cornell Medical College, New York, NY. mellingi@mskcc.org.
authors.forename: Ingo K
authors.initials: IK
authors.lastname: Mellinghoff
authors.affiliation: Elena I. Pentsova, Ronak H. Shah, Jiabin Tang, Adrienne Boire, Daoqi You, Samuel Briggs, Antonio Omuro, Xuling Lin, Martin Fleisher, Christian Grommes, Katherine S. Panageas, Fanli Meng, S. Duygu Selcuklu, Shahiba Ogilvie, Natalie Distefano, Larisa Shagabayeva, Marc Rosenblum, Lisa M. DeAngelis, Agnes Viale, Ingo K. Mellinghoff, and Michael F. Berger, Memorial Sloan Kettering Cancer Center; Ingo K. Mellinghoff, Weill-Cornell Graduate School of Biomedical Sciences; and Michael F. Berger, Weill-Cornell Medical College, New York, NY.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Berger
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000134:cerebrospinal fluid* / Q000235:genetics; D002474:Cell-Free System; D004273:DNA, Neoplasm / Q000134:cerebrospinal fluid*; D005260:Female; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation
chemical_list: D004273:DNA, Neoplasm