In vivo differentiation and genomic evolution in adult male germ cell tumors

Germ cell tumors (GCTs) are the most common solid malignancy in young adult men, but the genes and genomic regions involved in their etiology are not fully defined. We report here an investigation of DNA copy number changes in GCTs using 1 Mb BAC arrays. As expected, 12p gain was the defining genomic alteration, occurring in 72/74 GCTs. Parallel expression profiling of these tumors identified potential oncogenes from gained regions (LYN and RAB25) and potential tumor suppressor genes in regions of loss (SYNPO2, TTC12, IGSF4, and EPB41L3). Notably, we observed specific genomic alterations associated with histology, including gain of 17p1l.2-q21.32 and loss of 2p25.3 in embryonal carcinoma, gain of 8p23.3-12 and loss of 5p15.33-35.3, 11q23.1-25, and 13q12.11-34 in seminoma, and gain of 1q31.3-42.3, 3p, 14q11.2-32.33, and 20q and loss of 8q11.1-23.1 in yolk sac tumors (YST). Many significant genes that mapped to these regions had previously been associated with specific histologies, such as EOMES (chr3) and BMP2 (chr20) in YST and SPRY2 (chr13) and SOX17 (chr8) in seminomas. Additionally, our results suggest a model in which histologic differentiation of GCTs may drive genomic evolution.