Abstract
Objective: Testicular germ cell tumors (TGCTs) represent the most prevalent solid malignancy in young adult males. Despite multimodal treatment advancements, the molecular drivers of their aggressive biological behavior and subtype-specific differences remain insufficiently understood. Methods: This integrative in silico study utilized the cBioPortal platform to analyze Cancer Genome Atlas Pan-Cancer Atlas dataset. We examined genomic, transcriptomic, and proteomic data from a cohort of 149 TGCT patients to characterize mutation frequencies and structural variants across seminoma and non-seminomatous germ cell tumor subtypes. Results: Our analysis identified three principal genes with significant alteration frequencies: KIT (13%), KRAS (8%), and PTMA (5%). KIT and KRAS mutations demonstrated a marked subtype-specific distribution, with KRAS mutations observed exclusively in seminomas. In contrast, PTMA alterations displayed a broader distribution across multiple histologies, including mixed germ cell tumors and embryonal carcinomas. Additionally, we identified structural variants in genes such as TTC28, ACOT7, and CMSS1, highlighting the complexity of the TGCT genomic landscape. Conclusion: Our findings underscore the utility of integrative multi-omics analysis in elucidating the molecular background of TGCTs. The distinct association of KRAS and KIT with the seminomatous lineage, alongside the broad histological distribution of PTMA, provides novel insights into tumor biology. These molecular signatures may contribute to improved diagnostic precision and the development of tailored therapeutic interventions for patients with TGCT.