PENK and pancreatic neoplasm: Additional tumor suppressor genes with reduced expression due to aberrant hypermethylation in pancreatic tumors are preproenkephalin (PENK, hypermethylated in 93.3% of the tumor samples analyzed), the suppressor of cytokine-signaling 1 gene (SOCS-1, in 57.1%), protocadherin 10 (PCDH10, in 60.9%), iroquois homeobox 4 (IRX4, in 64%), and reprimo (RPRM, in 57%), among others [51–55].