MicroRNA ‐371–373 cluster and methylome analysis suggests that a subset of ‘somatic‐type’ malignancies arising in germ cell tumors may originate in yolk sac tumor components

作者：João Lobo, Nuno Tiago Tavares, Diana Fonseca, Cármen Jerónimo, Rui Henrique, Nicolas Wyvekens, Yiying Yang, Matija Snuderl, Fiona Maclean, Jennifer Gordetsky, Christopher D.�M. Fletcher, Michelle S. Hirsch, Jason L. Hornick, Muhammad T. Idrees, Katrina Collins, Laura M. Warmke, Thomas M. Ulbright, Andrés Acosta · 发表于：The Journal of Pathology · 年份：2025 · DOI：10.1002/path.6412 · 被引用次数：15 · 研究领域：Testicular diseases and treatments、Ovarian cancer diagnosis and treatment、Multiple Myeloma Research and Treatments

Somatic-type malignancies (SMs) arising in germ cell tumors (GCTs) are aggressive neoplasms resistant to systemic treatment. Most are diagnosed in metastatic sites after chemotherapy; however, they have also been well-documented in primary testicular GCTs. Historically, SMs were thought to originate in components of teratoma that acquire molecular alterations equivalent to those that characterize their true somatic counterparts. However, recent studies have shown that SMs typically lack the hallmark molecular alterations seen in similar somatic tumors. Additionally, clinicopathologic and molecular data suggest that a subset may derive from yolk sac tumor (YST) rather than teratoma. In this study, we evaluated the relationship between conventional histological types of GCTs and SMs by comparing expression of microRNA (miR)-371-373 and genomic methylation profiles. A total of 96 samples (including multiple paired conventional GCT-SM samples from individual tumors) were assessed for miR-371-373 expression by RT-qPCR and genomic DNA methylation using a clinically validated assay. Expression of miR-371-373 was higher in conventional GCTs than in SMs (considered as a single category encompassing all histological subtypes). However, miR-371-373 expression was heterogeneous among SMs, with significantly higher levels in sarcomatoid YST (SYST) and glandular neoplasms than in other SMs. Genomic DNA methylation analysis showed that SMs (considered as a single category) did not form a di...