ArticleNature communications2022
Comprehensive genomic and epigenomic analysis in cancer of unknown primary guides molecularly-informed therapies despite heterogeneity.
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Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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29citing papers in PubMed
7.4field-weighted citation impact, top 2% of its field
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29 citing papers in PubMed, 59 citations in OpenAlex.
- Feasibility and value of genomic profiling in cancer of unknown primary: real-world evidence from prospective profiling study.Journal of the National Cancer Institute · 2023Trial
- Cancer of unknown primary: the evolution of tissue of origin identification in the artificial intelligence era.Biomarker research · 2026Review
- Management and survival of patients with cancer of unknown primary discussed by a French national multidisciplinary tumour board: a retrospective analysis.The Lancet regional health. Europe · 2026Article
- HER2 Protein Overexpression, mRNA Expression, and DNA Amplification Across Solid Tumors: Comparison of Next-Generation Sequencing-Based Assays With Immunohistochemistry.JCO precision oncology · 2026Article
- Rethinking cancer of unknown primary: from diagnostic challenge to targeted treatment.Nature reviews. Clinical oncology · 2025Review
- Whole genome sequencing improves tissue-of-origin diagnosis and treatment options for cancer of unknown primary.Nature communications · 2025Article
- Celebrating Ulrik Ringborg: Multi-Omics-Based Patient Stratification for Precision Cancer Treatment.Biomolecules · 2025Review
- Impact of whole genome sequencing on the care pathway for patients with cancer of unknown primary.ESMO open · 2025Article
- Advancements in Diagnostics and Therapeutics for Cancer of Unknown Primary in the Era of Precision Medicine.MedComm · 2025Review
- The Growth Modulation Index (GMI) as an Efficacy Outcome in Cancer Clinical Trials: A Scoping Review with Suggested Reporting Guidelines.Current oncology reports · 2025Article
- MicroRNA Signatures: Illuminating Minimal Residual Disease Monitoring in Juvenile Myelomonocytic Leukemia - A Review.Journal of hematology · 2025Review
- Integrated cytomembrane proteomics identifies EpCAM/MGST1 as therapeutic targets in metastatic laryngeal carcinoma.Frontiers in genetics · 2025Article
- Epidemiologic, histopathological, and prognostic analysis of cancer of unknown primary in an Iranian population.Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences · 2025Article
- A machine learning-based method for feature reduction of methylation data for the classification of cancer tissue origin.International journal of clinical oncology · 2024Article
- Exploring the molecular landscape of cancer of unknown primary: A comparative analysis with other metastatic cancers.Molecular oncology · 2024Article
- Metastatic renal cell carcinoma with occult primary: a multicenter prospective cohort.NPJ precision oncology · 2024Article
- [The collaborative project "Personalized medicine for oncology" (PM4Onco) as part of the Medical Informatics Initiative (MII)].Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz · 2024Article
- PD-L1 expression and microsatellite instability (MSI) in cancer of unknown primary site.International journal of clinical oncology · 2024Article
- MUC16: clinical targets with great potential.Clinical and experimental medicine · 2024Review
- A cfDNA methylation-based tissue-of-origin classifier for cancers of unknown primary.Nature communications · 2024Article
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Authors and funding
44 authors at 12 institutions in 1 country.
Lino Möhrmann *Department of Translational Medical Oncology, National Center for Tumor Diseases (NCT) Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany.ORCID 0000-0003-4650-6827
Maximilian Werner *Department of Translational Medical Oncology, National Center for Tumor Diseases (NCT) Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany.ORCID 0000-0003-0252-5057
Małgorzata Oleś *Computational Oncology Group, NCT Heidelberg and DKFZ, Heidelberg, Germany.ORCID 0000-0002-1520-1054
Andreas Mock *Department of Translational Medical Oncology, NCT Heidelberg and DKFZ, Heidelberg, Germany.ORCID 0000-0002-3332-9166
Sebastian Uhrig *Computational Oncology Group, NCT Heidelberg and DKFZ, Heidelberg, Germany.
Arne JahnCenter for Personalized Oncology, NCT Dresden and University Hospital Carl Gustav Carus, Faculty of Medicine and Technische Universität Dresden, Dresden, Germany.ORCID 0000-0003-1045-1908
Simon KreutzfeldtDepartment of Translational Medical Oncology, NCT Heidelberg and DKFZ, Heidelberg, Germany.ORCID 0000-0003-3278-4586
Martina FröhlichComputational Oncology Group, NCT Heidelberg and DKFZ, Heidelberg, Germany.
Barbara HutterComputational Oncology Group, NCT Heidelberg and DKFZ, Heidelberg, Germany.ORCID 0000-0002-9034-0329
Nagarajan ParamasivamComputational Oncology Group, NCT Heidelberg and DKFZ, Heidelberg, Germany.
Daniela RichterDepartment of Translational Medical Oncology, National Center for Tumor Diseases (NCT) Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Katja BeckMolecular Precision Oncology Program, NCT Heidelberg, Heidelberg, Germany.
Ulrike WinterMolecular Precision Oncology Program, NCT Heidelberg, Heidelberg, Germany.
Katrin PfützeMolecular Precision Oncology Program, NCT Heidelberg, Heidelberg, Germany.
Christoph E HeiligDepartment of Translational Medical Oncology, NCT Heidelberg and DKFZ, Heidelberg, Germany.ORCID 0000-0001-8869-1421
Veronica TeleanuDepartment of Translational Medical Oncology, NCT Heidelberg and DKFZ, Heidelberg, Germany.
Daniel B LipkaDepartment of Translational Medical Oncology, NCT Heidelberg and DKFZ, Heidelberg, Germany.ORCID 0000-0001-5081-7869
Marc ZapatkaDivision of Molecular Genetics, DKFZ, Heidelberg, Germany.
Dorothea HanfDepartment of Translational Medical Oncology, National Center for Tumor Diseases (NCT) Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Catrin ListDepartment of Translational Medical Oncology, National Center for Tumor Diseases (NCT) Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Michael AllgäuerInstitute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.ORCID 0000-0003-4518-7887
Roland PenzelInstitute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Gina RüterCharité Comprehensive Cancer Center, Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Ivan JelasCharité Comprehensive Cancer Center, Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Rainer HamacherDepartment of Medical Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany.ORCID 0000-0001-9655-1226
Johanna FalkenhorstDepartment of Medical Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany.
Sebastian WagnerDepartment of Medicine 2, Hematology/Oncology, Goethe University, Frankfurt, Germany.
Christian H BrandtsDepartment of Medicine 2, Hematology/Oncology, Goethe University, Frankfurt, Germany.
Melanie BoerriesInstitute of Medical Bioinformatics and Systems Medicine, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany.ORCID 0000-0002-3670-0602
Anna L IllertDKTK, Freiburg, Germany.
Klaus H MetzelerDepartment of Internal Medicine III, University Hospital, LMU Munich and Comprehensive Cancer Center, Munich, Germany.ORCID 0000-0003-3920-7490
C Benedikt WestphalenDepartment of Internal Medicine III, University Hospital, LMU Munich and Comprehensive Cancer Center, Munich, Germany.
Alexander DesukiUniversity Cancer Center Mainz, University Medical Center Mainz, Mainz, Germany.
Thomas KindlerUniversity Cancer Center Mainz, University Medical Center Mainz, Mainz, Germany.
Gunnar FolprechtCenter for Personalized Oncology, NCT Dresden and University Hospital Carl Gustav Carus, Faculty of Medicine and Technische Universität Dresden, Dresden, Germany.
Wilko WeichertInstitute of Pathology, Technical University Munich, Munich, Germany.
Benedikt BrorsDivision of Applied Bioinformatics, NCT Heidelberg and DKFZ, Heidelberg, Germany.ORCID 0000-0001-5940-3101
Albrecht StenzingerInstitute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Evelin SchröckCenter for Personalized Oncology, NCT Dresden and University Hospital Carl Gustav Carus, Faculty of Medicine and Technische Universität Dresden, Dresden, Germany.
Daniel HübschmannComputational Oncology Group, NCT Heidelberg and DKFZ, Heidelberg, Germany.ORCID 0000-0002-6041-7049
Peter HorakDepartment of Translational Medical Oncology, NCT Heidelberg and DKFZ, Heidelberg, Germany.ORCID 0000-0003-4536-9306
Christoph HeiningDepartment of Translational Medical Oncology, National Center for Tumor Diseases (NCT) Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Stefan FröhlingDepartment of Translational Medical Oncology, NCT Heidelberg and DKFZ, Heidelberg, Germany.ORCID 0000-0001-7907-4595
Hanno GlimmDepartment of Translational Medical Oncology, National Center for Tumor Diseases (NCT) Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany. hanno.glimm@nct-dresden.de.ORCID 0000-0003-4104-1135
Heidelberg University · DEGerman Cancer Research Center · DENational Center for Tumor Diseases · DEEssen University Hospital · DEGerman Cancer Society · DEGoethe University Frankfurt · DEHumboldt-Universität zu Berlin · DEJohannes Gutenberg University Mainz · DELMU Klinikum · DEUniversity of Freiburg · DETechnical University of Munich · DEUniversity Hospital Carl Gustav Carus · DE
Funding
No grant is acknowledged in the PubMed record.
Abstract
The benefit of molecularly-informed therapies in cancer of unknown primary (CUP) is unclear. Here, we use comprehensive molecular characterization by whole genome/exome, transcriptome and methylome analysis in 70 CUP patients to reveal substantial mutational heterogeneity with TP53, MUC16, KRAS, LRP1B and CSMD3 being the most frequently mutated known cancer-related genes. The most common fusion partner is FGFR2, the most common focal homozygous deletion affects CDKN2A. 56/70 (80%) patients receive genomics-based treatment recommendations which are applied in 20/56 (36%) cases. Transcriptome and methylome data provide evidence for the underlying entity in 62/70 (89%) cases. Germline analysis reveals five (likely) pathogenic mutations in five patients. Recommended off-label therapies translate into a mean PFS ratio of 3.6 with a median PFS1 of 2.9 months (17 patients) and a median PFS2 of 7.8 months (20 patients). Our data emphasize the clinical value of molecular analysis and underline the need for innovative, mechanism-based clinical trials.
Indexed as
Neoplasms, Unknown PrimaryEpigenomicsGenomicsHomozygoteHumansMutationSequence Deletion
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