Background
truncating germline mutation, malignant transformation, TET2 deficiency, human cancers, TET2
SOLID TUMORS, MALIGNANT TRANSFORMATION
Aberrant DNA methylation disturbs transcriptional regulation, predisposes cells to malignant transformation and is a hallmark of human cancers [The human ten–eleven translocation (TET) protein family comprises three members (TET1, TET2 and TET3) that share the same catalytic activity. TETs mediate the iterative oxidation of 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine (5-fC) and 5-carboxylcytosine (5-caC), initiating the demethylation of cytosine residues in DNA. Eventually, the methyl group can be removed and an unmodified cytosine restored. The structure and expression patterns of TET proteins are divergent. TET2, unlike TET1 and TET3, lacks the CpG-interacting CXXC zinc finger domain and is highly expressed in the hematopoietic system [Vitamin C has been shown to boost TET-mediated 5-mC oxidation steps in cultured cells and in vivo in mice [Vitamin C has been extensively studied as a potential cancer-preventive agent in the context of solid tumors, but the results have remained inconclusive [We have previously reported a family in which a heterozygous truncating germline mutation in The family provided us with a unique opportunity to examine the effects of dietary vitamin C supplementation in individuals with TET2 deficiency. Three unaffected 