Molecular events in germ cell tumours: linking chromosome-12 gain, acquisition of pluripotency and response to cisplatin.
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.
Korkola
James E
JE
Cell Biology Division, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. JEKorkola@lbl.gov
Houldsworth
Jane
J
Bosl
George J
GJ
Chaganti
R S K
RS
D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D002945:Cisplatin / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D006801:Humans; D008297:Male; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000473:pathology; D039904:Pluripotent Stem Cells / Q000187:drug effects*; D013736:Testicular Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D055815:Young Adult
D000970:Antineoplastic Agents; D002945:Cisplatin