ArticleNature communications2024
A cfDNA methylation-based tissue-of-origin classifier for cancers of unknown primary.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
47 citing papers in PubMed, 42 citations in OpenAlex.
- Dalpiciclib plus endocrine therapy in women with HRNature cancer · 2026Trial
- Systemic health impact of cancer-associated extracellular vesicles and particles.Nature reviews. Cancer · 2026Review
- Advancing the applications of liquid biopsies in oncology.Nature reviews. Genetics · 2026Review
- Occult Esophageal Squamous Cell Carcinoma Presenting as Bone-Predominant Carcinoma of Unknown Primary: A Case Report of a p40-Negative Vertebral Metastasis.Diagnostics (Basel, Switzerland) · 2026Article
- Cancer of unknown primary: the evolution of tissue of origin identification in the artificial intelligence era.Biomarker research · 2026Review
- DNA Methylation as a Programmable Information Layer: From Molecular Marks to Disease State Engineering.International journal of molecular sciences · 2026Review
- Integrative Epigenomics: Bioinformatics Strategies for Multi-Omics Data Analysis in Health and Disease.Epigenomes · 2026Review
- Integrative cfDNA profiling from low-pass whole-genome sequencing enables tissue-of-origin prediction in cancer.Molecular biomedicine · 2026Article
- Integrating artificial intelligence into cancers of unknown primary diagnosis and treatment.iScience · 2026Review
- A scalable deep-learning framework for cancer detection using cell-free DNA shallow whole-genome sequencing.Science advances · 2026Article
- Clinical validation of a multi-model blood cfDNA methylation assay for early-stage gastrointestinal cancer screening.Journal of advanced research · 2026Article
- Review
- TiSMeD: A tissue-specific methylation and expression database for biomarker and translational applications.Molecular therapy. Nucleic acids · 2026Article
- Breaking news from ESMO 2025: liquid biopsy novelties in gastrointestinal cancer.The journal of liquid biopsy · 2026Article
- From Spatial Epigenomes to Clinical Diagnostics: Integrative Methylomics Across Scales and Modalities.International journal of molecular sciences · 2026Review
- Long-read sequencing identifies aberrant fragmentation patterns linked to elevated cell-free DNA levels in cancer.Genome biology · 2026Article
- Longitudinal cell-free DNA methylome and fragmentome profiles in health uncover signatures of cell type and demographic origin.Genome medicine · 2026Article
- DNMT/TET Imbalance and Network-Level DNA Methylation Remodeling in Ovarian Aging: Mechanistic Perspectives.Biology · 2026Review
- Cell-free DNA methylome and fragmentome analysis for relapse monitoring of Ewing sarcoma.EMBO molecular medicine · 2026Article
- M-PACT leverages cell-free DNA methylomes to achieve robust classification of pediatric brain tumors.Nature cancer · 2026Article
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 1 country.
Funding
Abstract
Cancers of Unknown Primary (CUP) remains a diagnostic and therapeutic challenge due to biological heterogeneity and poor responses to standard chemotherapy. Predicting tissue-of-origin (TOO) molecularly could help refine this diagnosis, with tissue acquisition barriers mitigated via liquid biopsies. However, TOO liquid biopsies are unexplored in CUP cohorts. Here we describe CUPiD, a machine learning classifier for accurate TOO predictions across 29 tumour classes using circulating cell-free DNA (cfDNA) methylation patterns. We tested CUPiD on 143 cfDNA samples from patients with 13 cancer types alongside 27 non-cancer controls, with overall sensitivity of 84.6% and TOO accuracy of 96.8%. In an additional cohort of 41 patients with CUP CUPiD predictions were made in 32/41 (78.0%) cases, with 88.5% of the predictions clinically consistent with a subsequent or suspected primary tumour diagnosis, when available (23/26 patients). Combining CUPiD with cfDNA mutation data demonstrated potential diagnosis re-classification and/or treatment change in this hard-to-treat cancer group.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.