Molecular Characteristics and Clinical Significance of Germ Cell Tumors

Abstract

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.