Genomic analysis of spermatocytic tumors demonstrates recurrent molecular alterations in cases with malignant clinical behavior

作者：Sounak Gupta, Lynette M. Sholl, Yiying Yang, Adeboye O. Osunkoya, Jennifer Gordetsky, Kristine M. Cornejo, Květoslava Michalová, Fiona Maclean, Eugénia Dvindenko, Matija Snuderl, Michelle S. Hirsch, William J. Anderson, Ross Rowsey, Rafael E. Jiménez, John C. Cheville, Peter M. Sadow, Maurizio Colecchia, Costantino Ricci, Thomas M. Ulbright, Daniel M. Berney, Andrés Acosta · 发表于：The Journal of Pathology · 年份：2023 · DOI：10.1002/path.6210 · 被引用次数：21 · 研究领域：Testicular diseases and treatments、Epigenetics and DNA Methylation、Sperm and Testicular Function

Spermatocytic tumor (ST) is a rare type of germ cell tumor that occurs exclusively in the postpubertal testis and typically affects elderly men. Most STs are benign, but rare cases exhibit aggressive clinical behavior, often in association with transition to sarcomatoid histology. Limited molecular analyses have been performed on STs; therefore, their genomic and epigenomic features remain incompletely described. Twenty-seven samples from 25 individual patients were analyzed with a combination of DNA sequencing panels, genomic methylation profiling, SNP array, isochromosome (12p) [i(12p)] FISH, and immunohistochemistry. The series included five metastasizing tumors (three with sarcomatoid transformation, one anaplastic, and one conventional) and 20 non-metastasizing tumors (14 anaplastic and six conventional). Anaplastic tumors comprised a monomorphic population of intermediate-sized neoplastic cells, as previously described. Multiomic analyses demonstrated that there were two genomic subgroups of STs: one with diploid genomes and hotspot RAS/RAF variants and the other with global ploidy shift and absence of recurrent mutations. Relative gain of chromosome 9 was a consistent finding in both subgroups. A comparison of metastasizing and non-metastasizing cases demonstrated that aggressive behavior was associated with the acquisition of pathogenic TP53 mutations and/or relative gains of 12p/i(12p). In cases with sarcomatoid transformation, TP53 mutations seem to underlie the tra...