Nuclear protein in testis (NUT) carcinoma is a rare but highly aggressive carcinoma, driven by genetic rearrangement of the NUT midline carcinoma family member 1 (NUTM1) gene on chromosome 15q14. Recently, a tight link has been suggested between genetic abnormalities and subsequent metabolic and epigenetic dysregulation to drive the progression of malignant tumors. However, it remains elusive whether such reprogramming could contribute to the pathogenesis of NUT carcinoma. We herein report an autopsy case of NUT carcinoma arising in the retroperitoneum of a 31-year-old male. Notably, reprogramming of glycolytic metabolism and epigenetic histone modifications was observed in this unusual NUT carcinoma case, and this phenomenon was further confirmed by an in vitro cell culture model with bromodomain containing 4 (BRD4)-NUT overexpression. The rationale for documenting the case is based on our findings to reveal that metabolic and epigenetic reprogramming could be one of the contributing factors to the pathogenesis of NUT carcinoma, which could be exploitable as a novel therapeutic target for this rare and aggressive cancer type.

In pre-disposed individuals, a reprogramming of the hepatic lipid metabolism may support liver cancer initiation. We conducted a high-resolution mass spectrometry based untargeted lipidomics analysis of pre-diagnostic serum samples from a nested case-control study (219 liver cancer cases and 219 controls) within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. Out of 462 annotated lipids, 158 (34.2%) were associated with liver cancer risk in a conditional logistic regression analysis at a false discovery rate (FDR) <0.05. A chemical set enrichment analysis (ChemRICH) and co-regulatory set analysis suggested that 22/28 lipid classes and 47/83 correlation modules were significantly associated with liver cancer risk (FDR <0.05). Strong positive associations were observed for monounsaturated fatty acids (MUFA), triacylglycerols (TAGs) and phosphatidylcholines (PCs) having MUFA acyl chains. Negative associations were observed for sphingolipids (ceramides and sphingomyelins), lysophosphatidylcholines, cholesterol esters and polyunsaturated fatty acids (PUFA) containing TAGs and PCs. Stearoyl-CoA desaturase enzyme 1 (SCD1), a rate limiting enzyme in fatty acid metabolism and ceramidases seems to be critical in this reprogramming. In conclusion, our study reports pre-diagnostic lipid changes that provide novel insights into hepatic lipid metabolism reprogramming may contribute to a pro-cell growth and anti-apoptotic tissue environment and, in turn, support liver cancer initiation.