Fig. 4

Nonseminoma (NS) evolution. A model of the different steps in NS development from normal primordial germ cell (PGC)/gonocytes to metastasised NS is shown. The model is based on the available literature regarding early genome duplication, acquisition of extra copies of the short arm of chromosome 12, the pluripotent capacity of the embryonal carcinoma (EC),⁴ and the results from this study. Following initial whole-genome doubling, during puberty chromosome loss may be the predominant way to change the copy numbers in the formation of germ cell neoplasia in situ (GCNIS) cancer stem cell (yellow). GCNIS represent a polyclonal mixture of cells, some may remain dormant and others may progress to malignancy. The gain of copies of 12p (12p⁺⁺) is a hallmark of the precursor with invasive potential (light orange). Further losses and gains of chromosomes or chromosome fragments may contribute to the formation of the primary tumour with its distinct histological components (orange) and the typical metastases (purple). Somatic mutation appears to be limited and occurring at later stages. The metastases may also originate from precursor EC not detected in the primary tumour