Fig. 3
Evolution of nonseminoma (NS). Evolutionary trees for the different histological specimens for all cases are shown on this developmental model. Colouring of boxes is according to sample type: germ cell neoplasia in situ (GCNIS; yellow), precursor embryonal carcinoma (EC; light orange), primary tumour (dark orange) and metastasis (purple). The order and grouping of the samples is based on the similarities in allele and somatic DNA variant (SNV) profiles (as shown in Fig. 2 and Supplementary Fig. S7) and supported by TargetClone (Materials and methods section), and implementing the biological constraint for NS development that the differentiated components (teratoma (TE) and yolk sac tumour (YST)) originated from an EC-type precursor. Samples with comparable profiles are grouped together. In specific cases of samples with partially non-overlapping features (i.e. SNV and/or loss of heterozygosity (LOH)) without an immediate precursor, a non-identified precursor (GCNISx or ECx) was inserted at the branch point in the tree (T6107, T618). Similarly, to comply with the evidence that an EC is the precursor of TE and YST, a non-identified precursor ECx was introduced (T6107, T1382). Specific gains of LOH or SNV compared with their immediate precursor are indicated. *) indicates SNV present at very low read frequencies, suggesting polyclonality for GCNIS or the presence of a minor subclone in some of the primary tumour components of T3209. For case T1382, a minimal tree is presented with ordering of samples based on SNV only due to sequencing noise
