Genome-Wide Copy-Number Landscape of Germ Cell Tumors With Synchronous Conventional and “Somatic-Type” Malignancy Components

So-called “somatic-type” malignancies (SMs) of germ cell tumor (GCT) origin resemble malignant neoplasms that arise from true somatic tissue. Except for enrichment in TP53 pathway alterations, the mutational profile of GCTs with SMs does not significantly differ from that of typical GCTs. Prior studies have suggested that copy number alterations (CNAs) of SMs may differ from those of conventional GCTs, but comparative genome-wide CNA analyses of paired components of GCTs with SMs have not been previously performed. The objective of this study was to compare CNAs in paired SMs and conventional components of individual GCTs. Twenty-two paired samples from 11 tumors were included in the study (6 metastases, 4 testicular primaries, and 1 mediastinal primary). Each paired sample represented synchronous conventional GCT and SM components from the same tumor, without pretreatment and post-treatment or primary–metastatic comparisons. The molecularly studied conventional GCT components included: teratoma (n=7), teratoma and yolk sac tumor (n=1), teratoma and seminoma (n=1), and seminoma (n=2). The SM components included: embryonic-type neuroectodermal tumor (ENT; n=3), rhabdomyosarcoma (RMS; n=2), ENT and RMS (n=1), unclassified sarcoma (n=2), nephroblastoma (n=1), carcinoma, NOS (n=1), and acinar cell carcinoma (n=1). In most tumors (8/11; 73%), CNA profiles of the paired samples were similar. In the remaining 3 tumors (3/11; 27%), the CNA profiles showed noticeable differences, with a higher number of CNAs in SM. Two of these were metastatic and the remaining was a mediastinal primary. No highly recurrent CNAs were identified in the SM components. The similar CNA profiles of paired SMs and conventional GCTs reinforces their common clonal origin. The differences observed in a subset likely reflect earlier divergent evolution of the SM subclones, with CNAs possibly underlying tumor progression.