To test these effects genetically, we used CRISPR/Cas9 to generate gene knockouts (KO) of SDHB, the most frequently mutated subunit in SDH-null human cancers (Amar et al., 2007; Badenhop et al., 2004; Klein et al., 2008; Linehan and Ricketts, 2013). This evidence concerns the gene SDHB and cancer.