Abstract Testicular germ cell tumors (TGCTs) are the most common cancer in young men. Although cure rates for TGCT are generally high, due to the sensitivity of malignant testicular germ cells to platinum-based chemotherapies, this comes at the cost of an increased risk of metabolic syndrome, infertility and secondary cancer. Furthermore, there are limited options for patients who are platinum resistant, a group for whom the long-term survival rate is less than 15%. Improved targeted therapies for TGCT are predicated on a greater understanding of mutational profile of these tumours, including identification of driver mutations and pathways disrupted. We recently published the first large-scale analysis of whole exome sequencing of TGCTs (comprising 42 tumors), which revealed a uniformly low mutation rate; some ∼ten times lower than average rates observed in other adult solid tumors, consistent with the embryological origin of TGCT. Aside from mutations in the previously known driver gene KIT, no additional novel genes with mutation frequency greater than 15% were associated with tumorigenesis. In parallel The Cancer Genome Atlas consortium is sequencing an additional series of TGCTs. Given the apparent absence of high frequency driver genes aside from KIT, several lower frequency oncogenic pathways may exist, requiring identification through larger sample size studies and/or pooled analysis. Here we present meta-analysis across multiple datasets with variant calling re-processed through a consistent bioinformatic pipeline. We systemically searched for novel recurrent mutational events at three levels:- (i) driver genes (combined sample size was empowered to detect recurrent gene mutations of frequency >5% with 89% power), ii) pathway based associations and iii) focal copy number alterations. In addition we assessed for clinicopathological-molecular associations, with particular focus on mutational events distinguishing treatment responsive and resistant tumors. Comprehensive cataloguing of the mutational spectra, through analyses of our data in combination with other initiatives such as TCGA, is leading to increasing insights into this biology of this cancer. Citation Format: Kevin Litchfield, Richard S. Houlston, Robert Huddart, Brenda Summersgill, Janet Shipley, Clare Turnbull. Meta-analysis of whole exome sequencing data reveals the mutational spectrum of testicular germ cell tumors. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2986. doi:10.1158/1538-7445.AM2015-2986