Harman Patil (Editor)

Tet methylcytosine dioxygenase 2

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Tet methylcytosine dioxygenase 2 (TET2) is a human gene. It resides at chromosome 4q24, in a region showing recurrent microdeletions and copy-neutral loss of heterozygosity (CN-LOH) in patients with diverse myeloid malignancies.

Contents

Function

TET2 encodes a protein that catalyzes the conversion of the modified DNA base methylcytosine to 5-hydroxymethylcytosine.

Clinical significance

Mutations in this gene were first identified in myeloid neoplasms with deletion or uniparental disomy at 4q24. TET2 may also be a candidate for active DNA demethylation, the catalytic removal of the methyl group added to the fifth carbon on the cytosine base.

Somatic TET2 mutations are frequently observed in myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), MDS/MPN overlap syndromes including chronic myelomonocytic leukaemia (CMML), acute myeloid leukaemias (AML) and secondary AML (sAML).

TET2 mutations have prognostic value in cytogenetically normal acute myeloid leukemia (CN-AML). "Nonsense" and "frameshift" mutations in this gene are associated with poor outcome on standard therapies in this otherwise favorable-risk patient subset.

WIT pathway

TET2 is mutated in 7%–23% of AML patients. Importantly, TET2 is mutated in a mutually exclusive manner with WT1, IDH1, and IDH2. TET2 can be recruited by WT1, a sequence-specific zinc finger transcription factor, to its target genes and activates WT1-target genes by converting methylcytosine into 5-hydroxymethylcytosine at the genes’ promoters. The WIT pathway might also be more broadly involved in suppressing tumor formation, as a number of non-hematopoietic malignancies appear to harbor mutations of WIT genes in a non-exclusive manner.

References

Tet methylcytosine dioxygenase 2 Wikipedia