Dataset Information

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.

SUBMITTER: Douville C

PROVIDER: S-EPMC10439243 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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

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

Cell reports. Medicine 20230807 8

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 ...[more]

PMID: 37552989

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Project description:Pediatric central nervous system tumors remain challenging to diagnose. Imaging approaches do not provide sufficient detail to discriminate between different tumor types, while the histopathological examination of tumor tissue shows high inter-observer variability. Recent studies have demonstrated the accurate classification of central nervous system tumors based on the DNA methylation profile of a tumor biopsy. However, a brain biopsy holds significant risk of bleeding and damaging the surrounding tissues. Liquid biopsy approaches analyzing circulating tumor DNA show high potential as an alternative and less invasive tool to study the DNA methylation pattern of tumors. Here, we explore the potential of classifying pediatric brain tumors based on methylation profiling of the circulating cell-free DNA (cfDNA) in cerebrospinal fluid (CSF). For this proof-of-concept study, we collected cerebrospinal fluid samples from 19 pediatric brain cancer patients via a ventricular drain placed for reasons of increased intracranial pressure. Analyses on the cfDNA showed high variability of cfDNA quantities across patients ranging from levels below the limit of quantification to 40 ng cfDNA per milliliter of CSF. Classification based on methylation profiling of cfDNA from CSF was correct for 7 out of 20 samples in our cohort. Accurate results were mostly observed in samples of high quality, more specifically those with limited high molecular weight DNA contamination. Interestingly, we show that centrifugation of the CSF prior to processing increases the fraction of fragmented cfDNA to high molecular weight DNA. In addition, classification was mostly correct for samples with high tumoral cfDNA fraction as estimated by computational deconvolution (> 40%). In summary, analysis of cfDNA in the CSF shows potential as a tool for diagnosing pediatric nervous system tumors especially in patients with high levels of tumoral cfDNA in the CSF. Further optimization of the collection procedure, experimental workflow and bioinformatic approach is required to also allow classification for patients with low tumoral fractions in the CSF.

Dataset Information

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

Publications

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

Similar Datasets

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