We also take lessons from our experience in treating primary central nervous system lymphoma (PCNSL) [13], and high dose intravenous methotrexate (MTX) is the most important and beneficial single agent in PCNSL [14–16], it acts as a potent inhibitor of dihydrofolate reductase (DHFR), and inhibition of thymidylate results in lack of DNA synthesis [17]. The gene discussed is DHFR; the disease is primary central nervous system lymphoma.