PTEN and Cowden disease: have shown that the KLLN promoter is hypermethylated in patients with Cowden syndrome without germline mutations in PTEN.[57] As the first predisposition gene for such syndrome, KLLN confers a high risk of breast, thyroid, and other cancers.[57] KLLN downregulation is significantly associated with high Gleason scores, indicating KLLN as a diagnostic or prognostic biomarker for advanced prostate carcinomas.[58] In breast cancer cells, Sankunny et al.