Copy number variations (CNV) and mutations are both critical drivers of tumorigenesis, but they are often analyzed separately and their synergistic effects remain unclear. Recent studies have shown composite mutations affecting the same gene show synergistic effects as cancer drivers. We reasoned that such synergistic effects may also occur for genomic alterations of different types, particularly CNVs and driver mutations. Herein, we seek to (1) identify the co-occurring driver mutations & CNVs, (2) show their synergistic effects in affecting the expression of cancer driver genes, and (3) validate their effects using the largest cancer DNA-Sequencing cohorts.