In the second mode, driver-upregulating mutations are predicted to create novel TFBS of transcriptional activators, such as novel ARID3A TFBS leading to upregulation of IER3 in colorectal cancer, LHX3 TFBS leading to upregulation of PARP2 in pancreas, TAED2 TFBS leading to upregulation of BCAR1 in ovary, and TCF12 TFBS leading to upregulation of PPM1D in breast cancer (Figure 6D). The gene discussed is LHX3; the disease is colorectal cancer.