ArticleNature2016
Genomic evolution and chemoresistance in germ-cell tumours.
Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
100 citing papers in PubMed, 1 synthesis or guideline pooled it, 168 citations in OpenAlex.
- Report From the International Society of Urological Pathology (ISUP) Consultation Conference on Molecular Pathology of Urogenital Cancers: IV: Current and Future Utilization of Molecular-Genetic Tests for Testicular Germ Cell Tumors.The American journal of surgical pathology · 2020Guideline
- Improved Tumor Purity Metrics in Next-generation Sequencing for Clinical Practice: The Integrated Interpretation of Neoplastic Cellularity and Sequencing Results (IINCaSe) Approach.Applied immunohistochemistry & molecular morphology : AIMMTrial
- Depth of response to primary POMB/ACE chemotherapy predicts survival in poor prognosis germ-cell tumours.British journal of cancer · 2026Article
- Comparative Molecular and Genetic Landscape of Gonadal Germ Cell Tumors: Insights from Testicular and Ovarian Neoplasms.Cancers · 2026Review
- Molecular pathology of testicular germ cell tumours: an update for practicing pathologists.Histopathology · 2026Review
- Spatial transcriptomics mapping of immune cell and TGFβ signalling pathway heterogeneity in testicular germ cell tumours.Andrology · 2026Article
- NanoString profiling of DNA repair and apoptosis genes in testicular germ cell tumours with divergent chemotherapy outcomes.Therapeutic advances in medical oncology · 2026Article
- Olaparib Response in a Patient With Platinum-Refractory Germ Cell Tumor Harboring a SomaticJCO precision oncology · 2026Article
- EMT and cancer stem cells: Drivers of therapy resistance and promising therapeutic targets.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2025Review
- [New insights from basic research on testicular germ cell tumors and updated tumorigenesis].Urologie (Heidelberg, Germany) · 2025Review
- A Thiopurine-like Mutagenic Process Defines TGCT Subtypes.bioRxiv : the preprint server for biology · 2025Article
- Exploring the molecular pathways of miRNAs in testicular cancer: from diagnosis to therapeutic innovations.Functional & integrative genomics · 2025Review
- Mitochondrial priming in therapy-induced senescence: implications for CAR-T/NK immunosenolytic therapy.Frontiers in immunology · 2025Review
- Deciphering the mysteries of MEG3 LncRNA and its implications in genitourinary cancers.Frontiers in oncology · 2025Review
- Driver mutations associated with signatures of platinum sensitivity in germ cell tumors.NPJ precision oncology · 2024Article
- Genomic landscape of adult testicular germ cell tumours in the 100,000 Genomes Project.Nature communications · 2024Article
- Single-molecule imaging of SWI/SNF chromatin remodelers reveals bromodomain-mediated and cancer-mutants-specific landscape of multi-modal DNA-binding dynamics.Nature communications · 2024Article
- CRISPR screens reveal convergent targeting strategies against evolutionarily distinct chemoresistance in cancer.Nature communications · 2024Article
- A rare germline BMP15 missense mutation causes hereditary ovarian immature teratoma in human.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- RAS/Mitogen-Activated Protein Kinase Signaling Pathway in Testicular Germ Cell Tumors.Life (Basel, Switzerland) · 2024Review
40 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 7 institutions in 3 countries.
Funding
Abstract
Germ-cell tumours (GCTs) are derived from germ cells and occur most frequently in the testes. GCTs are histologically heterogeneous and distinctly curable with chemotherapy. Gains of chromosome arm 12p and aneuploidy are nearly universal in GCTs, but specific somatic genomic features driving tumour initiation, chemosensitivity and progression are incompletely characterized. Here, using clinical whole-exome and transcriptome sequencing of precursor, primary (testicular and mediastinal) and chemoresistant metastatic human GCTs, we show that the primary somatic feature of GCTs is highly recurrent chromosome arm level amplifications and reciprocal deletions (reciprocal loss of heterozygosity), variations that are significantly enriched in GCTs compared to 19 other cancer types. These tumours also acquire KRAS mutations during the development from precursor to primary disease, and primary testicular GCTs (TGCTs) are uniformly wild type for TP53. In addition, by functional measurement of apoptotic signalling (BH3 profiling) of fresh tumour and adjacent tissue, we find that primary TGCTs have high mitochondrial priming that facilitates chemotherapy-induced apoptosis. Finally, by phylogenetic analysis of serial TGCTs that emerge with chemotherapy resistance, we show how TGCTs gain additional reciprocal loss of heterozygosity and that this is associated with loss of pluripotency markers (NANOG and POU5F1) in chemoresistant teratomas or transformed carcinomas. Our results demonstrate the distinct genomic features underlying the origins of this disease and associated with the chemosensitivity phenotype, as well as the rare progression to chemoresistance. These results identify the convergence of cancer genomics, mitochondrial priming and GCT evolution, and may provide insights into chemosensitivity and resistance in other cancers.
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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.