Molecular events in germ cell tumours: linking chromosome-12 gain, acquisition of pluripotency and response to cisplatin.

Overview

Germ cell tumours (GCTs) represent the leading cause of cancer-related morbidity and mortality in young men aged 18-35 years. Transformation of the cell of origin results in tumours with several unique properties. GCTs are characterized by gain of the short arm of chromosome 12 in almost all cases, a frequency of genomic alteration not seen in any other solid tumours. GCTs are truly pluripotent, giving rise to cells of somatic and extra-embryonic lineages, which results in tumours with a spectrum of differentiation that rivals that seen in normal embryogenesis and development. Despite the presence of genomic instability and many oncogenic changes, GCTs are highly curable, even in the metastatic setting, due to their extreme sensitivity to cisplatin-based chemotherapy. In this review we highlight some of the molecular events associated with the genesis, differentiation and chemotherapeutic response of these tumours, and discuss how these alterations are linked with biological features unique to germ cells.