PBRM1 and cancer: The over-expression of STAT2 +IRF9 did not change cell growth in culture (Figure 8B), however, overexpression of these ISGF3 components strongly suppressed tumor growth by PBRM1-deficient 786-O cells in a xenograft model (Figure 8C and D).Thus depletion of ISGF3 greatly enhanced tumor growth while its activation very potently blocked it, suggesting that ISGF3 is a central player in ccRCC tumor growth that is targeted by most of the cancer genes.