TET2andDNMT3AMutations in Human T-Cell Lymphoma

Abstract

Despite the poor prognosis of T-cell lymphomas, the genetic basis of these cancers is poorly defined.¹ We have found acquired TET2 mutations in both human myeloid cancers² and T-cell lymphoma.³ TET proteins are involved in the epigenetic control of transcription, at least through the oxidation of methylated cytosines and DNA demethylation.⁴ The catalytic activity of the TET proteins is inhibited by 2-hydroxyglutarate, an oncogenic metabolite produced by the mutated forms of the IDH1 and IDH2 enzymes. IDH mutations are observed in myeloid cancers, but involvement in T-cell lymphoma has not been reported. We investigated the status of these genes in a cohort of 96 patients with T-cell lymphoma, including 18 with TET2 mutations. Two IDH1 mutations were detected, in an extranodal cutaneous lymphoma and in a not-otherwise-specified lymphoma.