AB165. Whole-exome sequencing characterizes the landscape of somatic mutations and copy number variations in testicular germ cell tumor

Background Testicular germ cell tumor (TGCT) is the most common malignancy among young men. We conduct this study in order to further understand the genetic determinants of TGCT. Methods Eighteen TGCTs and matched normal controls were obtained from individuals newly diagnosed with TGCT in the hospital. Genomic DNAs were extracted from these samples and whole-exome sequencing was conducted by Hiseq 2000 platform. Copy number variations were called by exomeCNV based on the BWA alignments. Potential somatic substitutions and preliminary list of somatic indels were detected by the analyzed from our data. And these detected mutations were validated by Sanger sequencing. Results We identified a total of 77 nonsynonymous mutations with a uniformly low mutation rate of 0.14 mutations/Mb per tumor, on average. Notably, no somatic SNV was identified in 16.7% (3/18) of the tumors. Nevertheless, CTNNB1 and FZD10 were previously reported related to TGCT, potentially involved in the Wnt signaling pathway, contributing to the reprogram process during human embryonal carcinoma differentiation. Besides, KIAA1486 was the only recurrent gene identified in two tumors samples. With genetic evidence from United Kingdom, our study confirmed that gain of 12p (40/60; 66.7%) is the most frequent chromosomal aberration. Conclusions Our study uncovered a uniformly low mutation rate of these tumors, consistent with previous studies, supporting the embryonical origins of TGCT. Besides, the chromosomal aberrations were invariable presence, and no somatic SNV was identified in 16.7% (3/18) of the tumors, suggesting that chromosomal aberrations held a more critical role in the tumorigenesis of TGCT.