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TET2

From www.haematologyetc.co.uk


Gene affected:
TET2: Tet methylcytosine dioxygenase 2 gene
Clinical significance
Mutations affecting TET2 are frequent in haematological malignancies, there is unclear relevance to clinical outcome, although when present as a sole lesion in MDS outcome may be favourable. The prognostic significance of TET2 is highly influenced by co-occurring mutations.
Note TET2 is a frequently mutated gene in Age Related Clonal Change (ARCH) and in Clonal Haematopoieisis of Indeterminate Prognosis (CHIP). When detected as part of haematological neoplasia TET2 may persist following successful treatment. Interpretation therefore depends significantly on clinical context (see separate section)



Function of gene

TET2 is involved in the epigenetic regulation of DNA methylation. In haematology, mutations of TET2 particularly involve melodysplasia. It is also recognised that the WT1 (Wilms tumor 1) protein is involved in the regulation of TET2 binding to DNA. WT1 defects may therefore alter DNA methylation through a TET2-dependent route.


NGS panel gene coverage

Mutations are spread throughout the gene. This NGS panel covers the full coding sequence of the gene.Mutations are spread throughout the gene. This NGS panel covers the full coding sequence of TET2.




Occurrence:


Age related clonal haematopoiesis (frequently present with increasing age)
These somatic mutations carry increased risk of hamatological malignancy (similar to DNMT3A and ASXL1)
MDS (19%)
The prognostic significance of TET2 mutation is debated, the differences may reflect the various natures of mutations involved (including germ line and acquired) as well as the co-occurrence of other mutations. When present alone outcome may be favourable.
CMML (45%)
Generally favorable outcome but influenced by co-occurring mutations
MPN (10-15%)
Particularly PRV and in association with JAK2
AML (10%)
May have poor outcome, although not consistently demonstrated

Interactions:

  • Mutations of IDH1 and IDH2 genes are considered mutually exclusive with TET2 mutations
  • Associations: mutation of TET2 is frequently associated with other common myeloid mutations and outcome is significantly influenced by their presence (see separate text).



Links

GeneWiki link:
Gene Wiki entry for TET2
References
TET2 in CMML
TET2 in MPN
TET2 in AML
TET2 and hypomethylating agents
Difficulty in establishing prognostic value