SHMT2 activation induces SAM synthesis to promote DNA and histone methylation, leading to promoter silencing of previously unappreciated tumor suppressor genes, such as SAM and SH3 domain-containing protein 1 (SASH1) and protein tyrosine phosphatase receptor type M (PTPRM), and the initiation of lymphomagenesis (Parsa et al., 2020). The gene discussed is PTPRM; the disease is neoplasm.