Only a subset of tumor samples in our cohort had paired gene expression data (49/187 samples). This limited our ability to test for functional consequences of CBS hotspot mutations. Additional focused experiments involving transcriptome, copy number, and chromatin structure data should further clarify the regulatory and functional effects of the CBS mutations. We did not uncover a shared theme for the 23 significant non-CBS hotspots. Among the non-CBS hotspots, seven of them are intronic, one is downstream of a gene and the rest are intergenic. None of the genes associated with the hotspots are known cancer drivers. We did not observe any mutation hotspot near TERT, confirming that the reactivation of TERT is very rare in GC3. For the non-CBS hotspots that overlapped gene regions, focused functional validation experiments could be performed on a case-by-case basis.