Our analysis of splicing and gene expression changes associated with U2AF1 mutation across multiple cancer types has revealed alterations in 3′ splice site sequence recognition and highlights potential biological consequences through altered cancer genes, such as CTNNB1, PICALM, and CHCHD7. In addition, we have validated that at least some of these splicing alterations are direct consequences of U2AF1 mutation in transfection experiments. Here, CHCHD7 is linked to cancer.