{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T05:10:21Z","timestamp":1778649021972,"version":"3.51.4"},"reference-count":100,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Gonadal germ cell tumors (GCTs) arise in the testis and ovary from primordial germ cells. Despite shared origins, they display distinct molecular and genetic features. Understanding these differences is essential for clarifying tumor pathogenesis and improving diagnostic and therapeutic strategies. This review aims to compare these features and to better define the biological differences between testicular and ovarian GCTs. Methods: We reviewed cytogenetic alterations, epigenetic modifications, and somatic mutations reported in testicular and ovarian GCTs. Comparative analysis was performed to identify common and site-specific mechanisms. Results: Isochromosome 12p is a hallmark of testicular GCTs, while ovarian GCTs show diverse chromosomal changes. DNA methylation and other epigenetic marks differ by tumor subtype and gonadal origin. Somatic mutations affect pathways regulating cell cycle, pluripotency, and differentiation, with overlapping and unique patterns between testicular and ovarian tumors. Collectively, these findings define a molecular framework that explains both shared biology and gonadal-specific divergence in GCTs. Conclusions: Understanding molecular similarities and differences across gonadal GCTs can refine classification, guide biomarker discovery, and inform translational research. This comparative perspective highlights core pathogenetic mechanisms and gonadal-specific features relevant to clinical and experimental oncology.<\/jats:p>","DOI":"10.3390\/cancers18101554","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T12:05:22Z","timestamp":1778501122000},"page":"1554","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparative Molecular and Genetic Landscape of Gonadal Germ Cell Tumors: Insights from Testicular and Ovarian Neoplasms"],"prefix":"10.3390","volume":"18","author":[{"given":"Diana Elena","family":"Parteni","sequence":"first","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mihaela Camelia","family":"T\u00eernovanu","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3018-8011","authenticated-orcid":false,"given":"Elena","family":"\u021aarc\u0103","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alina","family":"Belu","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alina","family":"Jehac","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3994-6579","authenticated-orcid":false,"given":"Ludmila","family":"Lozneanu","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simona Eliza","family":"Giusca","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen","family":"Ungureanu","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eugenia","family":"Morosan","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7859-840X","authenticated-orcid":false,"given":"Elena","family":"Cojocaru","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1200\/JCO.23.01099","article-title":"Adolescent and Young Adult Germ Cell Tumors: Epidemiology, Genomics, Treatment, and Survivorship","volume":"42","author":"Travis","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e234","DOI":"10.1111\/j.1365-2605.2011.01157.x","article-title":"Dissecting the Molecular Pathways of (Testicular) Germ Cell Tumour Pathogenesis; from Initiation to Treatment-Resistance","volume":"34","author":"Looijenga","year":"2011","journal-title":"Int. J. Androl."},{"key":"ref_3","unstructured":"WHO Classification of Tumours Editorial Board (2023). Paediatric Tumours. WHO Classification of Tumours, IARC Publications. [5th ed.]."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Pinto, M.T., C\u00e1rcano, F.M., Vieira, A.G.S., Cabral, E.R.M., and Lopes, L.F. (2021). Molecular Biology of Pediatric and Adult Male Germ Cell Tumors. Cancers, 13.","DOI":"10.3390\/cancers13102349"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1038\/s41568-019-0178-9","article-title":"Human Germ Cell Tumours from a Developmental Perspective","volume":"19","author":"Oosterhuis","year":"2019","journal-title":"Nat. Rev. Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Pinto, M.T., Eiras Martins, G., Vieira, A.G.S., Galv\u00e3o, J.M.S., de P\u00e1dua Souza, C., Macedo, C.R.P.D., and Lopes, L.F. (2023). Molecular Biology of Pediatric and Adult Ovarian Germ Cell Tumors: A Review. Cancers, 15.","DOI":"10.3390\/cancers15112990"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1002\/ajmg.c.31562","article-title":"A Practical Guide for Evaluating Gonadal Germ Cell Tumor Predisposition in Differences of Sex Development","volume":"175","author":"Pyle","year":"2017","journal-title":"Am. J. Med. Genet. C Semin. Med. Genet."},{"key":"ref_8","first-page":"587","article-title":"Germ Cell and Other Tumors in Individuals with Differences in Sex Development","volume":"75","author":"Witchel","year":"2025","journal-title":"CA Cancer J. Clin."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1111\/j.1365-2605.2011.01245.x","article-title":"Gonadal and Extragonadal Germ Cell Tumours in the United States, 1973\u20132007","volume":"35","author":"Stang","year":"2012","journal-title":"Int. J. Androl."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1097\/01.ju.0000129571.13955.6b","article-title":"Epidemiological and Clinical Behavior of Prepubertal Testicular Tumors in Korea","volume":"172","author":"Lee","year":"2004","journal-title":"J. Urol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.jpurol.2021.06.006","article-title":"EAU-ESPU Pediatric Urology Guidelines on Testicular Tumors in Prepubertal Boys","volume":"17","author":"Stein","year":"2021","journal-title":"J. Pediatr. Urol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/S0301-2115(99)00141-4","article-title":"Mature Cystic Teratomas of the Ovary: Case Series from One Institution over 34 Years","volume":"88","author":"Ayhan","year":"2000","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_13","first-page":"EC11","article-title":"Clinicopathological Evaluation of 223 Cases of Mature Cystic Teratoma, Ovary: 25-Year Experience in a Single Tertiary Care Centre in India","volume":"11","author":"Rathore","year":"2017","journal-title":"J. Clin. Diagn. Res."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Cong, L., Wang, S., Yeung, S.Y., Lee, J.H.S., Chung, J.P.W., and Chan, D.Y.L. (2023). Mature Cystic Teratoma: An Integrated Review. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24076141"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"103224","DOI":"10.1016\/j.critrevonc.2021.103224","article-title":"Serum Tumour Markers in Germ Cell Tumours: From Diagnosis to Cure","volume":"159","author":"Pedrazzoli","year":"2021","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"21","DOI":"10.4103\/ua.ua_69_21","article-title":"The Core Four\u2014A Panel of Immunohistochemistry Markers to Diagnose and Subtype Testicular Germ Cell Tumors","volume":"14","author":"Ranjitha","year":"2022","journal-title":"Urol. Ann."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Cano Garcia, C., Barletta, F., Incesu, R.-B., Piccinelli, M.L., Tappero, S., Panunzio, A., Tian, Z., Saad, F., Shariat, S.F., and Antonelli, A. (2023). Survival of Testicular Pure Teratoma vs. Mixed Germ Cell Tumor Patients in Primary Tumor Specimens across All Stages. Cancers, 15.","DOI":"10.3390\/cancers15030694"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"802","DOI":"10.5306\/wjco.v13.i10.802","article-title":"Oncology and Reproductive Outcomes over 16 Years of Malignant Ovarian Germ Cell Tumors Treated by Fertility Sparing Surgery","volume":"13","author":"Rungoutok","year":"2022","journal-title":"World J. Clin. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Song, Z., Wang, Y., Zhou, Y., and Zhang, D. (2022). Nomograms to Predict the Prognosis in Malignant Ovarian Germ Cell Tumors: A Large Cohort Study. BMC Cancer, 22.","DOI":"10.1186\/s12885-022-09324-7"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/j.path.2019.01.005","article-title":"Germ Cell Tumors of the Female Genital Tract","volume":"12","author":"Euscher","year":"2019","journal-title":"Surg. Pathol. Clin."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1111\/andr.288","article-title":"Recent Trends in the Incidence of Testicular Germ Cell Tumors in the United States","volume":"3","author":"Ghazarian","year":"2015","journal-title":"Andrology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1111\/andr.12565","article-title":"Incidence of Testicular Tumor Subtypes According to the Updated WHO Classification, North Rhine-Westphalia, Germany 2008\u20132013","volume":"7","author":"Stang","year":"2019","journal-title":"Andrology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1093\/annonc\/mdw563","article-title":"The Role of Staging and Adjuvant Chemotherapy in Stage I Malignant Ovarian Germ Cell Tumors (MOGTs): The MITO-9 Study","volume":"28","author":"Mangili","year":"2017","journal-title":"Ann. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Sykes, J., Kaldany, A., and Jang, T.L. (2024). Current and Evolving Biomarkers in the Diagnosis and Management of Testicular Germ Cell Tumors. J. Clin. Med., 13.","DOI":"10.3390\/jcm13237448"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Gic\u0103, N., Peltecu, G., Chirculescu, R., Gic\u0103, C., Stoicea, M.C., Serbanica, A.N., and Panaitescu, A.M. (2022). Ovarian Germ Cell Tumors: Pictorial Essay. Diagnostics, 12.","DOI":"10.3390\/diagnostics12092050"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/s00428-025-04023-7","article-title":"Germ Cell Tumors in Children","volume":"486","author":"Bode","year":"2025","journal-title":"Virchows Arch."},{"key":"ref_27","first-page":"8","article-title":"Clinicopathological and Demographics Analysis of Testicular Tumors: A Single-Center Experience","volume":"58","year":"2025","journal-title":"Acta Haematol. Oncol. Turc."},{"key":"ref_28","first-page":"231","article-title":"Malignant Mixed Germ Cell Tumors of the Ovary: A Series of Rare Cases","volume":"20","author":"Goyal","year":"2019","journal-title":"J. Reprod. Infertil."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"408","DOI":"10.21037\/tau-20-1061","article-title":"Clinicopathological Characteristics and Survival Outcomes for Testicular Choriocarcinoma: A Population-Based Study","volume":"10","author":"Li","year":"2021","journal-title":"Transl. Androl. Urol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1097\/PAS.0b013e3182a2926e","article-title":"Clinicopathologic Analysis of Choriocarcinoma as a Pure or Predominant Component of Germ Cell Tumor of the Testis","volume":"38","author":"Paner","year":"2014","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1097\/PAS.0000000000000171","article-title":"Testicular Embryonal Carcinoma: A Morphologic Study of 180 Cases Highlighting Unusual and Unemphasized Aspects","volume":"38","author":"Kao","year":"2014","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1387\/ijdb.120202lm","article-title":"The Migration and Loss of Human Primordial Germ Stem Cells from the Hind Gut Epithelium towards the Gonadal Ridge","volume":"56","author":"Mamsen","year":"2012","journal-title":"Int. J. Dev. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1186\/s13287-025-04171-2","article-title":"The Establishment and Regulation of Human Germ Cell Lineage","volume":"16","author":"Yu","year":"2025","journal-title":"Stem Cell Res. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"dev201102","DOI":"10.1242\/dev.201102","article-title":"The Journey of a Generation: Advances and Promises in the Study of Primordial Germ Cell Migration","volume":"151","author":"Barton","year":"2024","journal-title":"Development"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1002\/rmb2.12283","article-title":"Mammalian Germ Cell Migration during Development, Growth, and Homeostasis","volume":"18","author":"Kanamori","year":"2019","journal-title":"Reprod. Med. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Oosterhuis, W., and Looijenga, L. (2017). Germ Cell Tumors from a Developmental Perspective: Cells of Origin, Pathogenesis, and Molecular Biology (Emerging Patterns). Pathology and Biology of Human Germ Cell Tumors, Springer.","DOI":"10.1007\/978-3-662-53775-6_3"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.humpath.2024.04.015","article-title":"Extragonadal Germ Cell Tumors: A Clinicopathologic Study with Emphasis on Molecular Features, Clinical Outcomes and Associated Secondary Malignancies","volume":"148","author":"Abdulfatah","year":"2024","journal-title":"Hum. Pathol."},{"key":"ref_38","first-page":"e51861","article-title":"Histopathological, Demographic, and Clinical Signatures of Medulla Oblongata Germ Cell Tumors: A Case Report With the Review of Literature","volume":"16","author":"Sato","year":"2024","journal-title":"Cureus"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1111\/j.1365-2605.2007.00793.x","article-title":"Why Human Extragonadal Germ Cell Tumours Occur in the Midline of the Body: Old Concepts, New Perspectives","volume":"30","author":"Oosterhuis","year":"2007","journal-title":"Int. J. Androl."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1093\/neuonc\/noac021","article-title":"Transcriptome and Methylome Analysis of CNS Germ Cell Tumor Finds Its Cell-of-Origin in Embryogenesis and Reveals Shared Similarities with Testicular Counterparts","volume":"24","author":"Takami","year":"2022","journal-title":"Neuro Oncol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"De Felici, M., and Klinger, F.G. (2021). PI3K\/PTEN\/AKT Signaling Pathways in Germ Cell Development and Their Involvement in Germ Cell Tumors and Ovarian Dysfunctions. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22189838"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2636","DOI":"10.1038\/s41467-023-38378-9","article-title":"Integrated Genomic Analysis Reveals Aberrations in WNT Signaling in Germ Cell Tumors of Childhood and Adolescence","volume":"14","author":"Xu","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1880","DOI":"10.1038\/sj.onc.1206302","article-title":"Expression Profile of Genes from 12p in Testicular Germ Cell Tumors of Adolescents and Adults Associated with i(12p) and Amplification at 12p11.2\u2013P12.1","volume":"22","author":"Rodriguez","year":"2003","journal-title":"Oncogene"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1038\/nature06403","article-title":"Nanog Safeguards Pluripotency and Mediates Germline Development","volume":"450","author":"Chambers","year":"2007","journal-title":"Nature"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1186\/s13287-024-03724-1","article-title":"NANOG Controls Testicular Germ Cell Tumour Stemness through Regulation of MIR9-2","volume":"15","author":"Cardenas","year":"2024","journal-title":"Stem Cell Res. Ther."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Von Eyben, F.E., and Parraga-Alava, J. (2020). Meta-Analysis of Gene Expressions in Testicular Germ Cell Tumor Histologies. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21124487"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Cuevas-Estrada, B., Montalvo-Casimiro, M., Munguia-Garza, P., R\u00edos-Rodr\u00edguez, J.A., Gonz\u00e1lez-Barrios, R., and Herrera, L.A. (2023). Breaking the Mold: Epigenetics and Genomics Approaches Addressing Novel Treatments and Chemoresponse in TGCT Patients. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24097873"},{"key":"ref_48","first-page":"3105","article-title":"Genetic Analysis of Ovarian Germ Cell Tumors by Comparative Genomic Hybridization","volume":"58","author":"Riopel","year":"1998","journal-title":"Cancer Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/0090-8258(92)90004-3","article-title":"DNA Ploidy of Ovarian Dysgerminomas: Correlation with Clinical Outcome","volume":"44","author":"Palmquist","year":"1992","journal-title":"Gynecol. Oncol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.cancergencyto.2004.02.010","article-title":"Evaluation of Genomic Changes in a Large Series of Malignant Ovarian Germ Cell Tumors\u2014Relation to Clinicopathologic Variables","volume":"155","author":"Kildal","year":"2004","journal-title":"Cancer Genet. Cytogenet."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1210\/er.2012-1045","article-title":"Molecular Characteristics of Malignant Ovarian Germ Cell Tumors and Comparison With Testicular Counterparts: Implications for Pathogenesis","volume":"34","author":"Kraggerud","year":"2013","journal-title":"Endocr. Rev."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.ygyno.2018.08.013","article-title":"The Genetic Landscape of 87 Ovarian Germ Cell Tumors","volume":"151","author":"Busschaert","year":"2018","journal-title":"Gynecol. Oncol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1002\/(SICI)1098-2264(199605)16:1<15::AID-GCC2>3.0.CO;2-6","article-title":"Deletion of 1p36 in Childhood Endodermal Sinus Tumors by Two-Color Fluorescence in Situ Hybridization: A Pediatric Oncology Group Study","volume":"16","author":"Perlman","year":"1996","journal-title":"Genes Chromosomes Cancer"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1002\/gcc.20363","article-title":"Imbalances of Chromosome Arm 1p in Pediatric and Adult Germ Cell Tumors Are Caused by True Allelic Loss: A Combined Comparative Genomic Hybridization and Microsatellite Analysis","volume":"45","author":"Zahn","year":"2006","journal-title":"Genes Chromosomes Cancer"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1002\/1096-911X(20010101)36:1<61::AID-MPO1016>3.0.CO;2-0","article-title":"Fine Mapping of a Tumour Suppressor Candidate Gene Region in 1p36.2-3, Commonly Deleted in Neuroblastomas and Germ Cell Tumours","volume":"36","author":"Abel","year":"2001","journal-title":"Med. Pediatr. Oncol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1111\/his.15090","article-title":"Primary Germ Cell Tumours of the Mediastinum: A Review with Emphasis on Diagnostic Challenges","volume":"84","author":"Fichtner","year":"2024","journal-title":"Histopathology"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1111\/andr.12814","article-title":"P53 and MDM2 Expression in Primary and Metastatic Testicular Germ Cell Tumors: Association with Clinical Outcome","volume":"8","author":"Lobo","year":"2020","journal-title":"Andrology"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Nicu, A.-T., Medar, C., Chifiriuc, M.C., Gradisteanu Pircalabioru, G., and Burlibasa, L. (2022). Epigenetics and Testicular Cancer: Bridging the Gap Between Fundamental Biology and Patient Care. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.861995"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"82","DOI":"10.3892\/etm.2025.12832","article-title":"Mechanisms of Cisplatin Sensitivity and Resistance in Testicular Germ Cell Tumors and Potential Therapeutic Agents (Review)","volume":"29","author":"Zhan","year":"2025","journal-title":"Exp. Ther. Med."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Nicu, A.-T., Ionel, I.P., Stoica, I., Burlibasa, L., and Jinga, V. (2024). Recent Advancements in Research on DNA Methylation and Testicular Germ Cell Tumors: Unveiling the Intricate Relationship. Biomedicines, 12.","DOI":"10.3390\/biomedicines12051041"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"39452","DOI":"10.1038\/s41598-025-22918-y","article-title":"Changes in Methylation Associated with Development of Metabolic Syndrome in Testicular Cancer Patients Treated with Cisplatin Chemotherapy","volume":"15","author":"Wojewodzic","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Nu\u00f1ez-Corona, D., Contreras-Sanz\u00f3n, E., Puente-Rivera, J., Arreola, R., Camacho-Nuez, M., Cruz Santiago, J., Estrella-Parra, E.A., Torres-Romero, J.C., L\u00f3pez-Camarillo, C., and Alvarez-S\u00e1nchez, M.E. (2023). Epigenetic Factors and ncRNAs in Testicular Cancer. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241512194"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1038\/s41416-023-02453-1","article-title":"Targeting Oncogenic microRNAs from the miR-371~373 and miR-302\/367 Clusters in Malignant Germ Cell Tumours Causes Growth Inhibition through Cell Cycle Disruption","volume":"129","author":"Bailey","year":"2023","journal-title":"Br. J. Cancer"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Angeles, A., Khazamipour, N., Dhillon, G., Janfaza, S., Oo, H.Z., Ozgun, G., Moeen, A., Nichols, C., Kollmannsberger, C., and Carey, M.S. (2025). Matching Plasma and Tissue miRNA Expression Analysis to Detect Viable Ovarian Germ Cell Tumors. PLoS ONE, 20.","DOI":"10.1371\/journal.pone.0322477"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1186\/s12964-025-02250-8","article-title":"MicroRNA-371\u2013373 Cluster Extracellular Vesicle-Based Communication in Testicular Germ Cell Tumors","volume":"23","author":"Tavares","year":"2025","journal-title":"Cell Commun. Signal"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1038\/s41420-021-00588-9","article-title":"Integrated Analysis of High-Throughput Sequencing Data Reveals the Key Role of LINC00467 in the Invasion and Metastasis of Testicular Germ Cell Tumors","volume":"7","author":"Bo","year":"2021","journal-title":"Cell Death Discov."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1007\/s11033-024-10083-w","article-title":"LINC00470 Promotes Malignant Progression of Testicular Germ Cell Tumors","volume":"51","author":"Liu","year":"2024","journal-title":"Mol. Biol. Rep."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2210","DOI":"10.1002\/ijc.35385","article-title":"Induction of SOX17 with Stimulation of WNT, TGF-Beta, and FGF Signaling Drives Embryonal Carcinomas into the Yolk-Sac Tumor Lineage Resulting in Increased Cisplatin Resistance","volume":"156","author":"Kotthoff","year":"2025","journal-title":"Int. J. Cancer"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Schmidtova, S., Kalavska, K., Liskova, V., Plava, J., Miklikova, S., Kucerova, L., Matuskova, M., Rojikova, L., Cierna, Z., and Rogozea, A. (2021). Targeting of Deregulated Wnt\/\u03b2-Catenin Signaling by PRI-724 and LGK974 Inhibitors in Germ Cell Tumor Cell Lines. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22084263"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1038\/s41379-020-00668-8","article-title":"Methylation Profiles of Imprinted Genes Are Distinct between Mature Ovarian Teratoma, Complete Hydatidiform Mole, and Extragonadal Mature Teratoma","volume":"34","author":"Kato","year":"2021","journal-title":"Mod. Pathol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1007\/s00428-023-03491-z","article-title":"Mature and Immature Ovarian Teratomas Share Methylation Profiles of Imprinted Genes: A MS-MLPA Analysis","volume":"482","author":"Kato","year":"2023","journal-title":"Virchows Arch."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1038\/s41416-018-0277-5","article-title":"Differences in DNA Methylation Profiles by Histologic Subtype of Paediatric Germ Cell Tumours: A Report from the Children\u2019s Oncology Group","volume":"119","author":"Williams","year":"2018","journal-title":"Br. J. Cancer"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Nestler, T., Schoch, J., Belge, G., and Dieckmann, K.-P. (2023). MicroRNA-371a-3p-The Novel Serum Biomarker in Testicular Germ Cell Tumors. Cancers, 15.","DOI":"10.3390\/cancers15153944"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.euo.2020.11.004","article-title":"Utility of Serum miR-371a-3p in Predicting Relapse on Surveillance in Patients with Clinical Stage I Testicular Germ Cell Cancer","volume":"4","author":"Lobo","year":"2021","journal-title":"Eur. Urol. Oncol."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Yodkhunnatham, N., Pandit, K., Puri, D., Yuen, K.L., and Bagrodia, A. (2024). MicroRNAs in Testicular Germ Cell Tumors: The Teratoma Challenge. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25042156"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Lobo, J., Nunes, S.P., Gillis, A.J.M., Barros-Silva, D., Miranda-Gon\u00e7alves, V., van den Berg, A., Cantante, M., Guimar\u00e3es, R., Henrique, R., and Jer\u00f3nimo, C. (2019). XIST-Promoter Demethylation as Tissue Biomarker for Testicular Germ Cell Tumors and Spermatogenesis Quality. Cancers, 11.","DOI":"10.3390\/cancers11091385"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"e16082","DOI":"10.1016\/j.heliyon.2023.e16082","article-title":"Long Non-Coding RNA TTTY14 Promotes Cell Proliferation and Functions as a Prognostic Biomarker in Testicular Germ Cell Tumor","volume":"9","author":"Cao","year":"2023","journal-title":"Heliyon"},{"key":"ref_78","first-page":"1091","article-title":"Crosstalk between Meg3 and miR-1297 Regulates Growth of Testicular Germ Cell Tumor through PTEN\/PI3K\/AKT Pathway","volume":"8","author":"Yang","year":"2016","journal-title":"Am. J. Transl. Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"56271","DOI":"10.1039\/C7RA12131H","article-title":"Long Non-Coding RNA Expression Profiles Predict Clinical Phenotypes of Seminoma and Yolk Sac Tumor","volume":"7","author":"Li","year":"2017","journal-title":"RSC Adv."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Barchi, M., Bielli, P., Dolci, S., Rossi, P., and Grimaldi, P. (2021). Non-Coding RNAs and Splicing Activity in Testicular Germ Cell Tumors. Life, 11.","DOI":"10.3390\/life11080736"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1111\/andr.12616","article-title":"New Insights into Germ Cell Tumor Genomics","volume":"7","author":"Lafin","year":"2019","journal-title":"Andrology"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2189","DOI":"10.1038\/s41467-020-15768-x","article-title":"Genomic Landscape of Platinum Resistant and Sensitive Testicular Cancers","volume":"11","author":"Loveday","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Onorato, A., Guida, E., Colopi, A., Dolci, S., and Grimaldi, P. (2024). RAS\/Mitogen-Activated Protein Kinase Signaling Pathway in Testicular Germ Cell Tumors. Life, 14.","DOI":"10.20944\/preprints202401.1820.v1"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.cancergen.2019.10.002","article-title":"Aberrant Epigenetic Inactivation of RASSF1A and MGMT Gene and Genetic Mutations of KRAS, cKIT and BRAF in Indian Testicular Germ Cell Tumours","volume":"241","author":"Ahmad","year":"2020","journal-title":"Cancer Genet."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Cabral, E.R.M., Pacanhella, M.F., Lengert, A.V.H., Dos Reis, M.B., Leal, L.F., de Lima, M.A., da Silva, A.L.V., Pinto, I.A., Reis, R.M., and Pinto, M.T. (2023). Somatic Mutation Detection and KRAS Amplification in Testicular Germ Cell Tumors. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1133363"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"3392","DOI":"10.1016\/j.celrep.2018.05.039","article-title":"Integrated Molecular Characterization of Testicular Germ Cell Tumors","volume":"23","author":"Shen","year":"2018","journal-title":"Cell Rep."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1038\/nature20596","article-title":"Genomic Evolution and Chemoresistance in Germ-Cell Tumours","volume":"540","author":"Zack","year":"2016","journal-title":"Nature"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1038\/nrurol.2016.107","article-title":"The Genomic Landscape of Testicular Germ Cell Tumours: From Susceptibility to Treatment","volume":"13","author":"Litchfield","year":"2016","journal-title":"Nat. Rev. Urol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"725","DOI":"10.3892\/or.2015.4402","article-title":"A Novel Somatic MAPK1 Mutation in Primary Ovarian Mixed Germ Cell Tumors","volume":"35","author":"Zou","year":"2016","journal-title":"Oncol. Rep."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1093\/biolre\/ioab052","article-title":"Whole-Exome Sequencing Reveals Potential Germline and Somatic Mutations in 60 Malignant Ovarian Germ Cell Tumors\u2020","volume":"105","author":"Chen","year":"2021","journal-title":"Biol. Reprod."},{"key":"ref_91","first-page":"153","article-title":"Molecular Genetics of Testicular Germ Cell Tumors","volume":"2","author":"Sheikine","year":"2012","journal-title":"Am. J. Cancer Res."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Steinmacher, S., Brucker, S.Y., K\u00f6lle, A., Kr\u00e4mer, B., Sch\u00f6ller, D., and Rall, K. (2021). Malignant Germ Cell Tumors and Their Precursor Gonadal Lesions in Patients with XY-DSD: A Case Series and Review of the Literature. Int. J. Environ. Res. Public Health, 18.","DOI":"10.3390\/ijerph18115648"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Lobo, J., Jer\u00f3nimo, C., and Henrique, R. (2020). Cisplatin Resistance in Testicular Germ Cell Tumors: Current Challenges from Various Perspectives. Cancers, 12.","DOI":"10.3390\/cancers12061601"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1007\/s00345-016-1898-z","article-title":"Platinum-Refractory Germ Cell Tumors: An Update on Current Treatment Options and Developments","volume":"35","author":"Oing","year":"2017","journal-title":"World J. Urol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"24191","DOI":"10.1038\/s41598-024-74192-z","article-title":"Dysgerminomas: Germ Cell Tumors Exhibit High Expression of PD-L1 and Associated with High TILs and Good Prognosis","volume":"14","author":"Alwosaibai","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"21794","DOI":"10.18632\/oncotarget.15585","article-title":"Prognostic Role of Programmed-Death Ligand 1 (PD-L1) Expressing Tumor Infiltrating Lymphocytes in Testicular Germ Cell Tumors","volume":"8","author":"Chovanec","year":"2017","journal-title":"Oncotarget"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/bjc.2015.244","article-title":"Frequent PD-L1 Expression in Testicular Germ Cell Tumors","volume":"113","author":"Fankhauser","year":"2015","journal-title":"Br. J. Cancer"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1093\/annonc\/mdx680","article-title":"Phase II Trial of Pembrolizumab in Patients with Platinum Refractory Germ-Cell Tumors: A Hoosier Cancer Research Network Study GU14-206","volume":"29","author":"Adra","year":"2018","journal-title":"Ann. Oncol."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Kalavska, K., Schmidtova, S., Chovanec, M., and Mego, M. (2020). Immunotherapy in Testicular Germ Cell Tumors. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.573977"},{"key":"ref_100","first-page":"1","article-title":"Response to Anti-Programmed Cell Death Protein-1 Antibodies in Men Treated for Platinum Refractory Germ Cell Cancer Relapsed after High-Dose Chemotherapy and Stem Cell Transplantation","volume":"76","author":"Lasitschka","year":"2017","journal-title":"Eur. J. Cancer"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/10\/1554\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T04:20:49Z","timestamp":1778646049000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/10\/1554"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,11]]},"references-count":100,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["cancers18101554"],"URL":"https:\/\/doi.org\/10.3390\/cancers18101554","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,11]]}}}