Chromosome 3p25.3 Gain Is Associated With Cisplatin Resistance and Is an Independent Predictor of Poor Outcome in Male Malignant Germ Cell Tumors Article Swipe
Dennis M. Timmerman
,
Thomas F. Eleveld
,
Sruthi Sriram
,
Lambert C. J. Dorssers
,
Ad Gillis
,
Silvia Schmidtova
,
Katarína Kaľavská
,
Harmen J.G. van de Werken
,
Christoph Oing
,
Friedemann Honecker
,
Michal Mego
,
Leendert H. J. Looijenga
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1200/jco.21.02809
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1200/jco.21.02809
PURPOSE Cisplatin is the main systemic treatment modality for male type II germ cell tumors (GCTs). Although generally very effective, 5%-10% of patients suffer from cisplatin-resistant disease. Identification of the driving mechanisms of resistance will enable improved risk stratification and development of alternative treatments. METHODS We developed and characterized cisplatin-resistant GCT cell line models and compared their molecular characteristics with patient samples with cisplatin resistance and/or a poor clinical outcome. Subsequently, the association between the overlapping genetic features and clinical data was assessed. Finally, we used Cox regression to determine the prognostic relevance of these features within the currently used risk classification. RESULTS Gain of chromosome 3p25.3 was detected in all cisplatin-resistant cell lines, and copy number of this region correlated with the level of resistance (R = 0.96, P = 1.5e-04). Gain of this region was detected at low frequencies in primary tumors and at higher frequencies in relapsed and/or cisplatin-resistant tumors. Chromosome 3p25.3 gain was associated with shorter progression-free survival and overall survival, with the strongest association observed in nonseminomas excluding pure teratomas. 3p25.3 gain was more frequently observed in tumors with yolk sac tumor histology and predicted adverse outcome independent of the International Germ Cell Cancer Collaborative Group risk classification and the presence of TP53/ MDM2 alterations. CONCLUSION On the basis of both in vitro analyses and clinical data, we found 3p25.3 to be strongly associated with cisplatin resistance and poor clinical outcome in male type II GCTs. Using genomic profiling, 3p25.3 status could help to improve risk stratification in male patients with type II GCT. Further characterization of this locus and underlying mechanisms of resistance is warranted to guide development of novel treatment approaches for cisplatin-resistant disease.
Related Topics
Concepts
Cisplatin
Medicine
Oncology
Germ cell tumors
Internal medicine
Testicular Germ Cell Tumor
Testicular cancer
Cancer research
Cancer
Chemotherapy
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1200/jco.21.02809
- https://ascopubs.org/doi/pdfdirect/10.1200/JCO.21.02809?role=tab
- OA Status
- hybrid
- Cited By
- 26
- References
- 30
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4224264396
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4224264396Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1200/jco.21.02809Digital Object Identifier
- Title
-
Chromosome 3p25.3 Gain Is Associated With Cisplatin Resistance and Is an Independent Predictor of Poor Outcome in Male Malignant Germ Cell TumorsWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2022Year of publication
- Publication date
-
2022-04-20Full publication date if available
- Authors
-
Dennis M. Timmerman, Thomas F. Eleveld, Sruthi Sriram, Lambert C. J. Dorssers, Ad Gillis, Silvia Schmidtova, Katarína Kaľavská, Harmen J.G. van de Werken, Christoph Oing, Friedemann Honecker, Michal Mego, Leendert H. J. LooijengaList of authors in order
- Landing page
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https://doi.org/10.1200/jco.21.02809Publisher landing page
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-
https://ascopubs.org/doi/pdfdirect/10.1200/JCO.21.02809?role=tabDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
hybridOpen access status per OpenAlex
- OA URL
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https://ascopubs.org/doi/pdfdirect/10.1200/JCO.21.02809?role=tabDirect OA link when available
- Concepts
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Cisplatin, Medicine, Oncology, Germ cell tumors, Internal medicine, Testicular Germ Cell Tumor, Testicular cancer, Cancer research, Cancer, ChemotherapyTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
26Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 9, 2024: 5, 2023: 10, 2022: 2Per-year citation counts (last 5 years)
- References (count)
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30Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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