Seq-ing the SINEs of central nervous system tumors in cerebrospinal fluid

Christopher Douville; Samuel Curtis; Mahmoud Summers; Tej D. Azad; Jordina Rincon-Torroella; Yuxuan Wang; Austin Mattox; Bracha Avigdor; Jonathan Dudley; Joshua Materi; Divyaansh Raj; Sumil Nair; Debarati Bhanja; Kyle Tuohy; Lisa Dobbyn; Maria Popoli; Janine Ptak; Nadine Nehme; Natalie Silliman; Cherie Blair; Kathy Judge; Gary L. Gallia; Mari Groves; Christopher M. Jackson; Eric M. Jackson; John Laterra; Michael Lim; Debraj Mukherjee; Jon Weingart; Jarushka Naidoo; Carl Koschmann; Natalya Smith; Karisa C. Schreck; Carlos A. Pardo; Michael Glantz; Matthias Holdhoff; Kenneth W. Kinzler; Nickolas Papadopoulos; Bert Vogelstein; Chetan Bettegowda

doi:10.1016/j.xcrm.2023.101148

Seq-ing the SINEs of central nervous system tumors in cerebrospinal fluid

Christopher Douville, Samuel Curtis, Mahmoud Summers, Tej D. Azad, Jordina Rincon-Torroella, Yuxuan Wang, Austin Mattox, Bracha Avigdor, Jonathan Dudley, Joshua Materi, Divyaansh Raj, Sumil Nair, Debarati Bhanja, Kyle Tuohy, Lisa Dobbyn, Maria Popoli, Janine Ptak, Nadine Nehme, Natalie Silliman, Cherie BlairKathy Judge, Gary L. Gallia, Mari Groves, Christopher M. Jackson, Eric M. Jackson, John Laterra, Michael Lim, Debraj Mukherjee, Jon Weingart, Jarushka Naidoo, Carl Koschmann, Natalya Smith, Karisa C. Schreck, Carlos A. Pardo, Michael Glantz, Matthias Holdhoff, Kenneth W. Kinzler, Nickolas Papadopoulos, Bert Vogelstein, Chetan Bettegowda

Research output: Contribution to journal › Article › peer-review

Abstract

It is often challenging to distinguish cancerous from non-cancerous lesions in the brain using conventional diagnostic approaches. We introduce an analytic technique called Real-CSF (repetitive element aneuploidy sequencing in CSF) to detect cancers of the central nervous system from evaluation of DNA in the cerebrospinal fluid (CSF). Short interspersed nuclear elements (SINEs) are PCR amplified with a single primer pair, and the PCR products are evaluated by next-generation sequencing. Real-CSF assesses genome-wide copy-number alterations as well as focal amplifications of selected oncogenes. Real-CSF was applied to 280 CSF samples and correctly identified 67% of 184 cancerous and 96% of 96 non-cancerous brain lesions. CSF analysis was considerably more sensitive than standard-of-care cytology and plasma cell-free DNA analysis in the same patients. Real-CSF therefore has the capacity to be used in combination with other clinical, radiologic, and laboratory-based data to inform the diagnosis and management of patients with suspected cancers of the brain.

Original language	English (US)
Article number	101148
Journal	Cell Reports Medicine
Volume	4
Issue number	8
DOIs	https://doi.org/10.1016/j.xcrm.2023.101148
State	Published - Aug 15 2023

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.xcrm.2023.101148

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Douville, C., Curtis, S., Summers, M., Azad, T. D., Rincon-Torroella, J., Wang, Y., Mattox, A., Avigdor, B., Dudley, J., Materi, J., Raj, D., Nair, S., Bhanja, D., Tuohy, K., Dobbyn, L., Popoli, M., Ptak, J., Nehme, N., Silliman, N., ... Bettegowda, C. (2023). Seq-ing the SINEs of central nervous system tumors in cerebrospinal fluid. Cell Reports Medicine, 4(8), Article 101148. https://doi.org/10.1016/j.xcrm.2023.101148

Douville, C, Curtis, S, Summers, M, Azad, TD, Rincon-Torroella, J , Wang, Y, Mattox, A, Avigdor, B, Dudley, J, Materi, J, Raj, D, Nair, S, Bhanja, D, Tuohy, K, Dobbyn, L, Popoli, M, Ptak, J, Nehme, N, Silliman, N, Blair, C, Judge, K, Gallia, GL , Groves, M , Jackson, CM , Jackson, EM , Laterra, J, Lim, M, Mukherjee, D , Weingart, J, Naidoo, J, Koschmann, C, Smith, N, Schreck, KC , Pardo, CA, Glantz, M, Holdhoff, M , Kinzler, KW , Papadopoulos, N , Vogelstein, B & Bettegowda, C 2023, 'Seq-ing the SINEs of central nervous system tumors in cerebrospinal fluid', Cell Reports Medicine, vol. 4, no. 8, 101148. https://doi.org/10.1016/j.xcrm.2023.101148

@article{3de41cb4e3054045bbd3d8830609baf6,

title = "Seq-ing the SINEs of central nervous system tumors in cerebrospinal fluid",

abstract = "It is often challenging to distinguish cancerous from non-cancerous lesions in the brain using conventional diagnostic approaches. We introduce an analytic technique called Real-CSF (repetitive element aneuploidy sequencing in CSF) to detect cancers of the central nervous system from evaluation of DNA in the cerebrospinal fluid (CSF). Short interspersed nuclear elements (SINEs) are PCR amplified with a single primer pair, and the PCR products are evaluated by next-generation sequencing. Real-CSF assesses genome-wide copy-number alterations as well as focal amplifications of selected oncogenes. Real-CSF was applied to 280 CSF samples and correctly identified 67% of 184 cancerous and 96% of 96 non-cancerous brain lesions. CSF analysis was considerably more sensitive than standard-of-care cytology and plasma cell-free DNA analysis in the same patients. Real-CSF therefore has the capacity to be used in combination with other clinical, radiologic, and laboratory-based data to inform the diagnosis and management of patients with suspected cancers of the brain.",

author = "Christopher Douville and Samuel Curtis and Mahmoud Summers and Azad, {Tej D.} and Jordina Rincon-Torroella and Yuxuan Wang and Austin Mattox and Bracha Avigdor and Jonathan Dudley and Joshua Materi and Divyaansh Raj and Sumil Nair and Debarati Bhanja and Kyle Tuohy and Lisa Dobbyn and Maria Popoli and Janine Ptak and Nadine Nehme and Natalie Silliman and Cherie Blair and Kathy Judge and Gallia, {Gary L.} and Mari Groves and Jackson, {Christopher M.} and Jackson, {Eric M.} and John Laterra and Michael Lim and Debraj Mukherjee and Jon Weingart and Jarushka Naidoo and Carl Koschmann and Natalya Smith and Schreck, {Karisa C.} and Pardo, {Carlos A.} and Michael Glantz and Matthias Holdhoff and Kinzler, {Kenneth W.} and Nickolas Papadopoulos and Bert Vogelstein and Chetan Bettegowda",

note = "Publisher Copyright: {\textcopyright} 2023 The Author(s)",

year = "2023",

month = aug,

day = "15",

doi = "10.1016/j.xcrm.2023.101148",

language = "English (US)",

volume = "4",

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T1 - Seq-ing the SINEs of central nervous system tumors in cerebrospinal fluid

AU - Douville, Christopher

AU - Curtis, Samuel

AU - Summers, Mahmoud

AU - Azad, Tej D.

AU - Rincon-Torroella, Jordina

AU - Wang, Yuxuan

AU - Mattox, Austin

AU - Avigdor, Bracha

AU - Dudley, Jonathan

AU - Materi, Joshua

AU - Raj, Divyaansh

AU - Nair, Sumil

AU - Bhanja, Debarati

AU - Tuohy, Kyle

AU - Dobbyn, Lisa

AU - Popoli, Maria

AU - Ptak, Janine

AU - Nehme, Nadine

AU - Silliman, Natalie

AU - Blair, Cherie

AU - Judge, Kathy

AU - Gallia, Gary L.

AU - Groves, Mari

AU - Jackson, Christopher M.

AU - Jackson, Eric M.

AU - Laterra, John

AU - Lim, Michael

AU - Mukherjee, Debraj

AU - Weingart, Jon

AU - Naidoo, Jarushka

AU - Koschmann, Carl

AU - Smith, Natalya

AU - Schreck, Karisa C.

AU - Pardo, Carlos A.

AU - Glantz, Michael

AU - Holdhoff, Matthias

AU - Kinzler, Kenneth W.

AU - Papadopoulos, Nickolas

AU - Vogelstein, Bert

AU - Bettegowda, Chetan

PY - 2023/8/15

Y1 - 2023/8/15

N2 - It is often challenging to distinguish cancerous from non-cancerous lesions in the brain using conventional diagnostic approaches. We introduce an analytic technique called Real-CSF (repetitive element aneuploidy sequencing in CSF) to detect cancers of the central nervous system from evaluation of DNA in the cerebrospinal fluid (CSF). Short interspersed nuclear elements (SINEs) are PCR amplified with a single primer pair, and the PCR products are evaluated by next-generation sequencing. Real-CSF assesses genome-wide copy-number alterations as well as focal amplifications of selected oncogenes. Real-CSF was applied to 280 CSF samples and correctly identified 67% of 184 cancerous and 96% of 96 non-cancerous brain lesions. CSF analysis was considerably more sensitive than standard-of-care cytology and plasma cell-free DNA analysis in the same patients. Real-CSF therefore has the capacity to be used in combination with other clinical, radiologic, and laboratory-based data to inform the diagnosis and management of patients with suspected cancers of the brain.

AB - It is often challenging to distinguish cancerous from non-cancerous lesions in the brain using conventional diagnostic approaches. We introduce an analytic technique called Real-CSF (repetitive element aneuploidy sequencing in CSF) to detect cancers of the central nervous system from evaluation of DNA in the cerebrospinal fluid (CSF). Short interspersed nuclear elements (SINEs) are PCR amplified with a single primer pair, and the PCR products are evaluated by next-generation sequencing. Real-CSF assesses genome-wide copy-number alterations as well as focal amplifications of selected oncogenes. Real-CSF was applied to 280 CSF samples and correctly identified 67% of 184 cancerous and 96% of 96 non-cancerous brain lesions. CSF analysis was considerably more sensitive than standard-of-care cytology and plasma cell-free DNA analysis in the same patients. Real-CSF therefore has the capacity to be used in combination with other clinical, radiologic, and laboratory-based data to inform the diagnosis and management of patients with suspected cancers of the brain.

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DO - 10.1016/j.xcrm.2023.101148

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VL - 4

JO - Cell Reports Medicine

JF - Cell Reports Medicine

IS - 8

M1 - 101148

ER -

Seq-ing the SINEs of central nervous system tumors in cerebrospinal fluid

Abstract

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