Seq-ing the SINEs of central nervous system tumors in cerebrospinal fluid - Report - Real-CSF multi-cancer biomarker

Sep 24, 2026

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Douville et al. introduce Real-CSF, an analytic sequencing approach that detects central nervous system cancers by profiling genome-wide copy-number alterations from limited DNA available in cerebrospinal fluid. Short interspersed nuclear elements (SINEs) are PCR-amplified with a single primer pair and assessed by next-generation sequencing, enabling both broad copy-number assessment and focal oncogene amplification detection. Applied to 280 CSF samples, Real-CSF correctly identified 67% of cancerous and 96% of non-cancerous lesions, outperforming standard cytology and plasma cell-free DNA sensitivity in the same patients and supporting integration with clinical, radiologic, and laboratory data for diagnosis and management.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages12

Reading Time30 min

AccessFree to download

In brief

Summary

Introduction

Challenges in diagnosing CNS tumors from CSF

Limitations of current diagnostic approaches

Report Seq-ing the SINEs of central nervous system tumorsin cerebrospinal ﬂuid Graphical abstract Highlights Authors Christopher Douville, Samuel Curtis, Mahmoud Summers, ..., Nickolas Papadopoulos, Bert Vogelstein, Chetan Bettegowda Correspondence [cbetteg1@jhmi.edu](cbetteg1@jhmi.edu) In brief Douville et al. introduce Real-CSF—a molecular technique designed to identify copy-number alterations spread throughout the genome from limited starting material in cerebrospinal ﬂuid. Even though central nervous system cancers comprise a heterogeneous set of tumors, nearly all will contain copynumber alterations, making this a putative multi-cancer biomarker. d Limited DNA in the cerebrospinal ﬂuid (CSF) poses challenges for genetic techniques d Copy-number alterations are a feature of nearly all CNS cancers d Real-CSF works in limited starting material and identiﬁes copy-number alterations d Real-CSF can detect neoplasia in CSF across a heterogeneous set of CNS cancers Douville et al., 2023, Cell Reports Medicine 4, 101148 August 15, 2023 ª 2023 The Author(s) . [https://doi.org/10.1016/j.xcrm.2023.101148](https://doi.org/10.1016/j.xcrm.2023.101148) ll ll OPEN ACCESS Report Seq-ing the SINEs of central nervous system tumors in cerebrospinal ﬂuid Christopher Douville,1,2,3,4 Samuel Curtis,1,2,3,4 Mahmoud Summers,1,2,3,4 Tej D. Azad,5 Jordina Rincon-Torroella,1,2,3,4,5 Yuxuan Wang,1,2,3,4 Austin Mattox,1,2,3,4 Bracha Avigdor,1,2,3,4 Jonathan Dudley,1,2,3,4,6 Joshua Materi,5 Divyaansh Raj,5 Sumil Nair,5 Debarati Bhanja,7 Kyle Tuohy,7 Lisa Dobbyn,1,2,3,4 Maria Popoli,1,2,3,4 Janine Ptak,1,2,3,4 Nadine Nehme,1,2,3,4 Natalie Silliman,1,2,3,4 Cherie Blair,1,2,3,4 Kathy Judge,1,2,3,4 Gary L. Gallia,5 Mari Groves,5 Christopher M. Jackson,5 Eric M. Jackson,5 John Laterra,8 Michael Lim,9 Debraj Mukherjee,5 Jon Weingart,5 Jarushka Naidoo,10 Carl Koschmann,11 Natalya Smith,7 Karisa C. Schreck,1,8 Carlos A. Pardo,8 Michael Glantz,7 Matthias Holdhoff,1 Kenneth W. Kinzler,1,2,3,4 Nickolas Papadopoulos,1,2,3,4 Bert Vogelstein,1,2,3,4,12 and Chetan Bettegowda1,2,3,4,5,13,* 1Department of Oncology, The Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA 2The Ludwig Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA 3The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA 4Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA 5Department of Neurosurgery, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA 6Department of Pathology, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA 7Department of Neurosurgery, Pennsylvania State University, Hershey, PA, USA 8Department of Neurology, Johns Hopkins Medical Institutions, Baltimore, MD, USA 9Department of Neurosurgery, Stanford University, Palo Alto, CA, USA 10Department of Oncology, Beaumont Hospital, Dublin, Ireland 11Division of Pediatric Oncology, University of Michigan, Ann Arbor, MI, USA 12The Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA 13Lead contact *Correspondence: [cbetteg1@jhmi.edu](cbetteg1@jhmi.edu) [https://doi.org/10.1016/j.xcrm.2023.101](https://doi.org/10.1016/j.xcrm.2023.101)148 SUMMARY 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 ar

FAQs

What problem does Real-CSF address in diagnosing central nervous system tumors?

Reliable, quantitative biomarkers are limited, and conventional CSF cytology often requires larger volumes while sensitivity depends on tumor type. Real-CSF is designed to work with limited starting DNA in cerebrospinal fluid.

How does Real-CSF perform sequencing and what genomic features does it detect?

SINEs are PCR-amplified with a single primer pair and the PCR products are evaluated by next-generation sequencing. It assesses genome-wide copy-number alterations and can identify focal amplifications of selected oncogenes.

How did Real-CSF perform on CSF samples compared with standard approaches?

In 280 CSF samples, Real-CSF identified 67% of 184 cancerous lesions and 96% of 96 non-cancerous lesions. CSF analysis was reported as more sensitive than standard-of-care cytology and plasma cell-free DNA analysis in the same patients.

Sep 24, 2026

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