This could be because CAD requires ICAD for proper folding. In order to investigate the role of CAD, CAD was overexpressed in SUNE1 cells, but that did not result in significant changes in H 2O 2-induced MLL gene cleavage. Treatment with H 2O 2 clearly induces cleavages within the MLL gene which locates at 11q23, a common deletion site in NPC. Gene expression was confirmed by Western blotting and MLL gene cleavage was assessed by inverse polymerase chain reaction (IPCR). Transfections with hCAD, mCAD, mutant hCAD, or cotransfection with hCAD and mICAD, and cotransfection with mutant hCAD and mICAD were performed. SUNEI cells were treated with various concentrations of H 2O 2 for different period of time to ensure that cells undergo H 2O 2-induced MLL gene cleavage. In view of the role of oxidative stress in carcinogenesis and CAD activation, and since CAD was suggested to contribute to chromosome rearrangement in leukaemia, we hypothesise that oxidative stress-induced CAD activation could be one of the mechanisms that leads to chromosome rearrangements in NPC. CAD is the main enzyme that causes DNA fragmentation during apoptosis, and CAD is also implicated in promoting cell differentiation. Activation of CAD can be initiated by multiple agents, including oxidative stress, which is well implicated in carcinogenesis. Although the mechanism underlying the chromosome rearrangements in NPC is unclear, various mechanisms including activation of caspase-activated DNase (CAD) were proposed to contribute to chromosome rearrangements in leukaemia. Chromosome rearrangements are common among NPC patients. Nasopharyngeal carcinoma (NPC) is commonly found in Asia, especially among the Chinese ethnic group.