MutSig analysis25 identified MEN1 as the only statistically significant cancer driver gene across this pNET cohort, although previously described variants in a small number of other tumor suppressor genes were seen in multiple tumors (Figs. 1 and 2) including ATRX, DAXX, PTEN, YY1, and VHL. Private variants in 31 other genes were detected in single patients, some of which were clinically interesting as previously described predictive biomarkers for specific therapies, including bi-allelic inactivation of MSH2 and mono-allelic variants in genes such as RET, JAK2, FGFR3, and BRCA2 (Fig. 1). This evidence concerns the gene VHL and cancer.