GNMT and cancer: Glycine N-methyltransferase (GNMT) deficiency is a rare genetic condition leading to SAM over-production.43 The genetic knockout of Gnmt in mice increased hepatic SAM by over 40-fold.43 Moreover, Gnmt knockout mice demonstrated promoter methylation of tumor suppressor genes such as RASSF1 and SOCS2, which led to their transcriptional silencing.44 As a consequence, Gnmt knockout was associated with activation of oncogenic pathways and an increased incidence of hepatocellular carcinoma.44 Cancer cells have also been shown to boost SAM availability via promoting one-carbon metabolism.