Genetic analysis of germ cell tumors: current progress and future prospects

Abstract

Cytogenetic analysis of germ cell tumors (GCTs) has identified i(12p) as a specific cytogenetic abnormality identified in more than 80% of GCTs, present in all histologies, in primary and metastatic lesions, in testicular and extragonadal presentations, and in ovarian and sex cord stromal tumors. Other nonrandom numeric and structural chromosomal abnormalities have also been identified. Oncogene studies suggest a potential role for n-ras mutations in GCT transformation. The role of loss of tumor suppressor genes and increased genomic dosage of growth promoter genes remain areas of great interest. Leukemias and differentiated malignancies that arise in the setting of GCT appear to be clonally derived from GCT cells, with evidence of karyotypic progression and acquisition of other tumor-specific cytogenetic markers. Identification of i(12p) in poorly differentiated midline carcinomas of uncertain histogenesis can assist in the diagnosis of GCT. The presence of three or more copies of 12p may predict resistance to chemotherapy and portend a higher likelihood of treatment failure. Future cytogenetic studies in GCT promise to provide insight into the biology and treatment of all solid tumors, because GCTs are a model of chemotherapeutic responsiveness, cellular differentiation, and tumor clonal evolution.