PTEN and colorectal carcinoma: Global hypomethylation decreased by 10–40% in CRC compared to normal colonic tissue, being associated with genomic instability, while promoter hyper-methylation leads to repression of several tumor suppressor genes and their specific pathways (e.g., TP53, PI3K/PTEN/AKT/mTOR, TGFb/SMAD) [15].