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Special Issue Editor

Prof. Dr. Michal Mego

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Guest Editor

2nd Department of Oncology, Faculty of Medicine, Comenius University and National Cancer Institute, Klenova 1, 833 10 Bratislava, Slovakia
Interests: circulating tumor cells; breast cancer; testicular cancer

Special Issue Information

Dear Colleagues,

Germ cell tumors (GCT) belong to the most chemosensitive solid tumors and represent a model for a curable cancer. Cisplatin represents the mainstay in the treatment of GCTs. Cisplatin-based first line chemotherapy can cure about 70–80% of patients with disseminated testicular cancer. Salvage chemotherapy with standard dose cisplatin plus previously not utilized drugs will cure 20–25% of patients who were not initially cured with their induction chemotherapy.

Because of insufficient results in the treatment of poor-risk and relapsed/refractory GCTs, evaluation of new treatment strategies and new drugs with significant antitumor activity, as single-agent or combination treatments, remains a priority. Identification of new biomarkers and/or therapeutic targets remains one of the research goals as well.

This Special issue of IJMS is focused on advances in research of poor-risk and relapsed/refractory testicular germ cell tumor and articles that cover this topic, including preclinical research, biomarker research, and research that focuses on special subpopulations of patients are welcome.

Prof. Michal Mego
Guest Editor

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Keywords

testicular germ cell tumors
poor-risk
multiple relapsed/refractory
chemoresistance

Published Papers (2 papers)

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Research

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16 pages, 4270 KiB

Open AccessArticle

The Role of TP53 in Cisplatin Resistance in Mediastinal and Testicular Germ Cell Tumors

by Dennis M. Timmerman, Thomas F. Eleveld, Ad J. M. Gillis, Carlijn C. Friedrichs, Sanne Hillenius, Tessa L. Remmers, Sruthi Sriram and Leendert H. J. Looijenga

Int. J. Mol. Sci. 2021, 22(21), 11774; https://doi.org/10.3390/ijms222111774 - 29 Oct 2021

Cited by 11 | Viewed by 2268

Abstract

Germ cell tumors (GCTs) are considered to be highly curable; however, there are major differences in the outcomes related to histology and anatomical localization. GCTs originating from the testis are, overall, sensitive to platinum-based chemotherapy, whereas GCTs originating from the mediastinum show a worse response, which remains largely unexplained. Here, we address the differences among GCTs from two different anatomical locations (testicular versus mediastinal/extragonadal), with a specific focus on the role of the P53 pathway. It was recently shown that GCTs with TP53 mutations most often localize to the mediastinum. To elucidate the underlying mechanism, TP53 knock-out lines were generated in cisplatin-sensitive and -resistant clones of the representative 2102Ep cell line (wild-type TP53 testicular GCT) and NCCIT cell line (hemizygously mutated TP53, mutant TP53 mediastinal GCT). The full knock-out of TP53 in 2102Ep and resistant NCCIT resulted in an increase in cisplatin resistance, suggesting a contributing role for P53, even in NCCIT, in which P53 had been reported to be non-functional. In conclusion, these results suggest that TP53 mutations contribute to the cisplatin-resistant phenotype of mediastinal GCTs and, therefore, are a potential candidate for targeted treatment. This knowledge provides a novel model system to elucidate the underlying mechanism of clinical behavior and possible alternative treatment of the TP53 mutant and mediastinal GCTs. Full article

(This article belongs to the Special Issue Poor-Risk and Relapsed/Refractory Germ Cell Tumor)

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9 pages, 4271 KiB

Open AccessCase Report

Recurrence of a Mediastinal Germ-Cell Tumor as a Somatic-Type Malignancy: A Complex Case Report

by Caroline C. C. Hulsker, Mariëtte E. G. Kranendonk, Thomas F. Eleveld, Ad J. M. Gillis, Cornelis P. van de Ven, Natasha K. A. van Eijkelenburg, Niels P. van der Kaaij, Alida F. W. van der Steeg and Leendert H. J. Looijenga

Int. J. Mol. Sci. 2021, 22(17), 9310; https://doi.org/10.3390/ijms22179310 - 27 Aug 2021

Cited by 1 | Viewed by 2080

Abstract

Background and case: An adolescent male presented with a second mediastinal tumor 1.5 years after treatment of a proven malignant germ-cell tumor in that location. The differential diagnosis included a recurrent germ-cell tumor or a non-germ cell malignancy. Serum tumor markers alpha-fetoprotein (AFP) and human chorionic gonadotrophin (HCG) were negative. The first biopsy was not informative, and the second biopsy gave a broad differential diagnosis including secondary non-germ cell malignancy using histology and immunohistochemistry. DNA methylation profiling, RNA sequencing, and targeted microRNA371a-3p profiling was subsequently performed, without a supportive result. After resection of the tumor the definitive diagnosis yielded two secondary non-germ cell malignancies in the form of a leiomyosarcoma and a solitary neuro endocrine carcinoma (NEC). In spite of the differences between the molecular profiles of the initial germ-cell tumor, the leiomyosarcoma and large-cell NEC are clonally related, as determined by the presence of identical chromosomal breakpoints. The copy number profiles suggest an initial polyploidization step, followed by various independent chromosomal gains and losses. This case demonstrates that germ-cell tumors must be evaluated carefully, including molecularly, in which the non-germ cell malignancy is negative for miR-371a-3p, both in tissue as well as in serum, in contrast to the primary tumor. We conclude that the patient presented with a primary type II mediastinal GCT and, a year and a half later, followed by a leiomyosarcoma and a large-cell NEC presenting as two secondary somatic-type malignancies clonally related to the original GCT. Conclusions: Malignant germ-cell tumors are known to recur as a somatic-type malignancy in very rare cases. This case report illustrates the challenges faced in defining the nature and clonality of the secondary somatic-type malignancies. Full article

(This article belongs to the Special Issue Poor-Risk and Relapsed/Refractory Germ Cell Tumor)

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