Dear Editor, Apolipoprotein C2 (APOC2), an activator of lipoprotein lipase, participates in hydrolysis of triglycerides, very low-density lipoproteins, and high-density lipoproteins to release free fatty acids (FA). 1 FA oxidation has emerged as an important source of energy for cancer survival and growth. 2 Patterns of APOC2 genomics and transcriptomic alterations in cancer remained unexplored. Here, we characterize APOC2 deregulation in cancer by analyzing 176 studies (supplementary-methods).In 46706 samples of 34 different cancers (Table S1), amplification, mutation, and deep deletion were the main identified APOC2 alterations (Figure S1A). Approximately 1% (251 patients) had at least one genetic alteration in APOC2 with the highest frequency (9.72%) present in bladder cancer and gene amplification being the most common alteration. The highest frequency of deep deletions in APOC2 occurred in diffuse glioma (1.36%). APOC2 mutations occurred in 2.3% of non-melanoma skin cancer and at lower frequencies in other cancers (Table S2). Among the 26 different APOC2 missense and truncating mutations, two were previously reported in hypertriglyceridemia (Figure S1B; Tables S3 and S4).APOC2 was expressed at significantly higher levels in several malignancies (Figures 1 and S2), such as patient-derived glioblastoma stem cells (33.7-fold, p < 0.0001; Figure 1A), invasive ductal breast cancer (2.9fold, p < 0.0001; Figure 1B), centroblastic lymphoma (10.1fold, p < 0.0001; Figure 1C), early stage colorectal tumor (3.8-fold, p = 0.0001; Figure 1D), hypopharyngeal cancer (2.1-fold, p = 0.04; Figure 1E), clear cell renal cell carcinoma (5.9-fold, p < 0.001; Figure 1F), skin squamous cell carcinoma (2.3-fold, p = 0.023; Figure 1G), and gastric cancer (4.8-fold, p = 0.002; Figure 1H) compared with the corresponding normal tissues.