Fig. 1

Dissection of nonseminoma (NS). a NS may consist of multiple histological elements (examples case T1382, TE and EC; case T618, germ cell neoplasia in situ (GCNIS), OCT3/4 stained nuclei), which were each enriched by laser capture micro dissection. The primary NS was subjected to WGS and the purified components to targeted sequencing using Ion Torrent technology. b The results of the whole genome sequencing (WGS) are shown per case. Complete genomics (CG) somatic DNA variant (SNV) were retrieved from CG output files, and putative candidates were selected after visual inspection of the reads. SNV validation was performed by mutation-specific PCR, targeted DNA sequencing and/or RNA sequencing (Supplementary Table S4). Structural variants (SVs) were confirmed for selected cases using targeted sequencing. Mutations occurring near exon boundaries were evaluated for potential effect on splicing using Alamut Software. Details are provided in Supplementary Tables S4-S6. The bottom panel shows the number of purified histological components isolated and analysed for these cases. PBL peripheral blood leukocytes, NAP nonmalignant adjacent parenchyma. c The mutational profiles of these four NS were compared with the 30 COSMIC signatures described. The mutational signatures contributing significantly (>5%) are presented. In addition, the SNV of NS and SE cases from the Taylor-Weiner study (*)¹⁴ were pooled for tumour subtype and similarly analysed. The number of SNV used for the analysis is indicated below each bar. d, e Profiles of lesser allele frequencies (LAF) of heterozygote SNP and relative read frequencies of SNV derived from targeted sequencing of primary NS (red) and dissected EC components (green) are shown. SNV are presented as filled symbols (NS: yellow diamonds; EC: green squares). Positions are provided on chromosomes scaled according to size