TNFRSF10C CNV in patients with CRC is associated with distant metastatic disease. A high frequency of CGI methylation in the TNFRSF10C promoter results in inactivation of the gene and enhancement of tumor growth in most PC cell lines (except CFPAC-1). Inactivation of TNFRSF10C by CpG island (CGI) hypermethylation can play an important role in PC progression and be potentially useful as a diagnostic marker and a new therapeutic approach for PC.