ArticleClinical epigenetics2021
Methylated markers accurately distinguish primary central nervous system lymphomas (PCNSL) from other CNS tumors.
Article in Clinical epigenetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 17 citations in OpenAlex.
- Advances in molecular pathobiology of PCNSL - towards clinical implementation of novel diagnostics and therapeutics.Biomarker research · 2026Review
- Primary central nervous system lymphoma in the molecular era: genomic drivers, liquid biopsy, and targeted therapeutic strategies.Annals of hematology · 2026Review
- Liquid Biopsy and Epigenetic Signatures in AML, ALL, and CNS Tumors: Diagnostic and Monitoring Perspectives.International journal of molecular sciences · 2025Review
- Circulating tumor DNA in lymphoma: technologies and applications.Journal of hematology & oncology · 2025Review
- Liquid biopsy for improving diagnosis and monitoring of CNS lymphomas: A RANO review.Neuro-oncology · 2024Review
- A multicenter proof-of-concept study on deep learning-based intraoperative discrimination of primary central nervous system lymphoma.Nature communications · 2024Article
- Genes Selectively Expressed in Rat Organs.Current genomics · 2024Article
- Detecting aberrant DNA methylation in Illumina DNA methylation arrays: a toolbox and recommendations for its use.Epigenetics · 2023Article
- Diagnostic performance and prognostic value of circulating tumor DNA methylation marker in extranodal natural killer/T cell lymphoma.Cell reports. Medicine · 2023Article
- Progress of radiological‑pathological workflows in the differential diagnosis between primary central nervous system lymphoma and high‑grade glioma (Review).Oncology reports · 2023Article
- Radiomic features define risk and are linked to DNA methylation attributes in primary CNS lymphoma.Neuro-oncology advancesArticle
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundDefinitive diagnosis of primary central nervous system lymphoma (PCNSL) requires invasive surgical brain biopsy, causing treatment delays. In this paper, we identified and validated tumor-specific markers that can distinguish PCNSL from other CNS tumors in tissues. In a pilot study, we tested these newly identified markers in plasma.
resultsThe Methylation Outlier Detector program was used to identify markers in TCGA dataset of 48 diffuse large B-cell lymphoma (DLBCL) and 656 glioblastomas and lower-grade gliomas. Eight methylated markers clearly distinguished DLBCL from gliomas. Marker performance was verified (ROC-AUC of ≥ 0.989) in samples from several GEO datasets (95 PCNSL; 2112 other primary CNS tumors of 11 types). Next, we developed a novel, efficient assay called Tailed Amplicon Multiplexed-Methylation-Specific PCR (TAM-MSP), which uses two of the methylation markers, cg0504 and SCG3 triplexed with ACTB. FFPE tissue sections (25 cases each) of PCNSL and eight types of other primary CNS tumors were analyzed using TAM-MSP. TAM-MSP distinguished PCNSL from the other primary CNS tumors with 100% accuracy (AUC = 1.00, 95% CI 0.95-1.00, P < 0.001). The TAM-MSP assay also detected as few as 5 copies of fully methylated plasma DNA spiked into 0.5 ml of healthy plasma. In a pilot study of plasma from 15 PCNSL, 5 other CNS tumors and 6 healthy individuals, methylation in cg0504 and SCG3 was detectable in 3/15 PCNSL samples (20%).
conclusionThe Methylation Outlier Detector program identified methylated markers that distinguish PCNSL from other CNS tumors with accuracy. The high level of accuracy achieved by these markers was validated in tissues by a novel method, TAM-MSP. These studies lay a strong foundation for a liquid biopsy-based test to detect PCNSL-specific circulating tumor DNA.
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