Genomic characteristics revealed by targeted exon sequencing of testicular germ cell tumors in Japanese men

Objective To investigate the somatic mutation profiles of testicular germ cell tumors in Japanese men. Methods We analyzed the somatic missense mutation profile of testicular germ cell tumors among 21 Japanese men with seminoma (n = 14), pure embryonic carcinoma (n = 3) and mixed testicular germ cell tumor (n = 4) by targeted next-generation sequencing of 409 cancer-related genes covering 1.23 Mb of the genome. Results We identified a total of 22 missense mutations in 21 primary testicular germ cell tumor samples (0.89 mutations/Mb), of which seven mutations were confirmed to be absent from the germline. KIT:p.Asn822Tyr, KIT:p.Leu576Pro, PIK3CA:p.Glu542Lys and FBXW7:p.Arg505His were statistically and functionally potential. A total of 18 missense mutations were previously unknown in testicular germ cell tumors.PDGFRAamplification from one patient with seminoma was detected.KIT,BCR,PIK3CG,PIK3CAandPDGFRAmutations involved in aberrant signaling of theKIT-PI3K-AKTpathway was detected in 27.3% of detected mutations. Conclusions The present investigation identified a low mutation rate in testicular germ cell tumors among Asian patients, 18 novel mutations andPDGFRAamplification. Limitations of the present study are the small sample and missing normal DNA for some testicular germ cell tumors.

Automated summary

This study investigated somatic mutation profiles of testicular germ cell tumors in Japanese men and identified a low mutation rate, 18 novel mutations, and PDGFRA amplification. Mutations in genes such as KIT, BCR, PIK3CG, PIK3CA, and PDGFRA were found to be involved in aberrant signaling of the KIT-PI3K-AKT pathway.