[Molecular Characteristics and Clinical Significance of Germ Cell Tumors]

Germ cell tumors(GCT), which predominantly emerge in the early to middle teenage years among males, affect the pineal gland, followed by the neurohypophysis, often presenting with site-specific symptoms. Diagnosis hinges on imaging, tumor markers(HCG and AFP), and pathological evaluation. The radiation dose/coverage and chemotherapy intensity are tailored to the distinction between the germinoma and non-germinoma types. Surgical resection is reserved for residual non-germinomas. Biological investigations have revealed frequent mutations in the RAS, MAPK, and PI3K pathways, with no obvious structural variations. These mutations are more prevalent in germinomas than in non-germinomas. Germinomas exhibit a strikingly low methylation status across the genome, mirroring the state of primordial germ cells(PGC), deemed as the cells of origin. Mitosis/meiosis-related genes are highly expressed in germinoma, which is another supporting evidence of PGCs as cells of origin. In contrast, non-germinomas display transcriptomic features that differentiate them into tissue formation and organogenesis. Frequent copy number alterations are another hallmark of GCTs. Among these, 12p gain has been identified as a negative prognostic factor in non-germinomas. Pathologically confirmed tumor cell content serves as a poor prognostic indicator in germinomas and requires external validation as a reliable marker. Given the significant long-term sequelae stemming from treatment burdens in vulnerable young patients, a need for targeted therapy has arisen. Ongoing genomic studies are exploring the pathogenesis and uncovering potential leads for the establishment of precision medicine.