Origin of Extragonadal Versus Gonadal Seminomas.

423 Background: There is debate whether a primary seminoma of the anterior mediastinum originates from a stranded germ cell in the midline near the thymus as it migrates from the yolk sac to the gonad1 or from abnormal development of the thymic anlage during embryogenesis.2 We hypothesized that if extragonadal seminoma were to arise from an adult stem cell at an ectopic site rather than from an errant primordial germ cell (PGC), it would display a methylated imprint resembling that of thymic epithelial tumors, such as a thymoma, rather than that of a gonadal seminoma. Methods: We performed reduced representation bisulfite sequencing (RRBS) of FFPE DNA of testicular seminoma, anterior mediastinal seminoma, thymomas, atypical thymomas, and thymic carcinomas. Results: RRBS of testicular seminoma (n=1), anterior mediastinal seminoma (n=1), thymomas (n=2), atypical thymomas (n=2), and thymic carcinomas (n=2) showed that the methylated genetic imprint of an extragonadal seminoma clustered more closely to that of an atypical thymoma than that of testicular seminoma. Conclusions: Our preliminary RRBS results suggest that extragonadal seminoma may have a thymic rather than PGC origin. We plan to confirm these results by evaluating certain PGC-specific genetic biomarkers and epigenetic signatures in additional cases. References: 1. Dixon FJ, Moore RA. Testicular tumors: a clinicopathological study. Cancer 1953;6:427. 2. Schlumberger HG. Teratoma of the anterior mediastinum in the group of military age: a study of sixteen cases, and a review of theories of genesis. Arch Pathol 1946;41:398.