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Germ cell tumors were considered very heterogeneous and diverse, until recently. Researchers from the Erasmus MC, Rotterdam, the Netherlands, and the Princess Máxima Center for pediatric oncology have added structure by suggesting a subdivision in seven types of germ cell tumors. This division is relevant for basic and clinical research and contributes to optimal diagnostics and healthcare in the future.
Germ cell tumors constitute a diverse group of rare tumors, which occur in the testes, ovaries and also in other places. Some germ cell tumors exist prenatally, while others present during or after puberty. The majority is benign. Malignant germ cell tumor most frequently appear in the testicle of adolescent and young adult men. Fortunately, these are treatable; even when metastasized, survival rates are over 80 per cent.
Various germ cell tumors As the name suggests, germ cell tumors develop from germ cells: sperm cells, oocytes and theirprogenitors. When an oocyte is fertilized, the development of an embryo is initiated. The fertilized oocyte has the potential to become any other type of cell. Early in development cells lose this ability, and the number of cell types they may become is restricted. ‘However, in a new individual there need to be new germ cells that have the potential to become all cell types’, explains prof. dr. Leendert Looijenga (Princess Máxima Center and Erasmuc MC). ‘These cells carry the potential danger of become germ cell tumors by spontaneously starting embryonal development.’
Different molecular mechanisms need to prevent spontaneous embryonal development by germ cells, since these would result in tumors. Sometimes things go awry in one of these protective mechanisms. ‘Dependent on which mechanism is affected, we distinguished until recently five types of germ cell tumors’, says Looijenga. By prolonged studies Looijenga and his colleague prof. dr. Wolter Oosterhuis (Erasmus MC) gained new insights and expanded the amount of tumor types to seven. They described their finding in the scientific magazine Nature Reviews Cancer.
Expansion of the tumor types One of the newly described categories is type 0. ‘This is in fact an underdeveloped Siamese twin’, says Oosterhuis. ‘At the points of attachment of the Siamese twins, a second embryo manifests as germ cell tumor. The baby is born with the tumor.’
Type 0 and the other five, earlier described types differ from other types of cancer in that they do not arise as a result of mutations in the DNA, but are caused instead by failure of the mechanism that should prevent spontaneous embryonal development.
Germ cell tumor type VI is the only type that is caused by mutations in the DNA. Very seldom that occurs spontaneously in the body, but more often adult cells are genetically modified in the laboratory for therapeutic purposes, for instance regenerative medicines. ‘These cell may only be safely used, when we can prevent the development of germ cell tumor type IV’, states Looijenga.
The new insight into the development of germ cell tumors and the division based upon that constituted a solid ground for future epidemiologic, fundamental and clinical research. Moreover, the division is highly valuable in direct patient care. ‘Treatment sensitivity and also resistances can be mapped more reliably. This may contribute to improved treatments in the future,’ says Looijenga.