• What is TET2?
  • TET2 in Myelodysplastic Syndromes
  • TET2 Mutations
  • Clinical Trials

TET2

Tet methylcytosine dioxygenase 2 (TET2; also known as ten-eleven translocation 2) is a gene that codes for a protein involved in epigenetic regulation of myelopoeisis (Gene 2014; Solary et al. 2014). TET2 is a tumor suppressor, and so in cancer, loss of TET2 function, which can occur via TET2 mutation, TET2 deletion, or IDH1 or IDH2 mutation, can cause myeloid or lymphoid transformations (Solary et al. 2014). Mutations in TET2 have been found in MDS, AML, ALL, and other hematologic malignancies.​

Related Pathways

Contributors: Stephen A. Strickland, M.D., MSCI, Annette S. Kim, M.D., Ph.D.

Suggested Citation: Strickland, S., A. Kim. 2015. TET2. My Cancer Genome https://www.padiracinnovation.org/content/disease/myelodysplastic-syndromes/tet2/?tab=0 (Updated December 4).

Last Updated: December 4, 2015

TET2 in Myelodysplastic Syndromes

TET2 mutations occur in 18.7% of MDS (COSMIC). TET2 mutations are observed in all types of MDS, and they tend to co-occur with SRFS2 in chronic myelomonocytic leukemia (CMML), a subtype of MDS (Cazzola, Della Porta, and Malcovati 2013). TET2 mutations are believed to cause loss of function (Solary et al. 2014). TET2 is a tumor suppressor gene, and so loss-of-function mutations support the abnormal hematopoiesis observed in MDS (Solary et al. 2014). These mutations are found spread throughout the gene.

TET2 mutations are a neutral or favorable prognostic biomarker (Bejar et al. 2011; Kosminder et al. 2009; NCCN 2014). However, Bejar et al. (2014) observed that TET2 mutations predict shorter overall survival following hematopoietic stem cell transplantation.​

Contributors: Stephen A. Strickland, M.D., MSCI, Annette S. Kim, M.D., Ph.D.

Suggested Citation: Strickland, S., A. Kim. 2014. TET2 in Myelodysplastic Syndromes. My Cancer Genome https://www.padiracinnovation.org/content/disease/myelodysplastic-syndromes/tet2/ (Updated September 23).

Last Updated: September 23, 2014

TET2 Mutations in Myelodysplastic Syndromes

Properties
Location of mutations TET2 gene on 4q24
Frequency of TET2 mutations in MDS 18.7% (COSMIC)
Implications for Targeted Therapeutics
Response to bromodomain inhibitors, DOT1L inhibitors, or other targeted epigenetic therapies Unknown at this timea
Response to spliceosome-targeting therapies Unknown at this timeb
Response to Ras-targeting therapies Unknown at this timec

TET2 mutations are a neutral or favorable prognostic biomarker (Bejar et al. 2011; Kosminder et al. 2009; NCCN 2014). However, Bejar et al. (2014) observed that TET2 mutations predict shorter overall survival following hematopoietic stem cell transplantation.

a Bromodomain (BRD2, BRD3, BRD4, and BRDt) inhibitors and DOT1L inhibitors are in phase I studies in hematologic malignancies (Abdel-Wahab and Levine 2013). In addition, several other epigenetic targeted therapies, targeting IDH1/IDH2, EZH2, LSD1, or UTX/JMJD3, are in development (Abdel-Wahab and Levine 2013).

b Drugs targeting the spliceosome are in development; these drugs alter gene expression or affect alternative splicing in ways that inhibit cancer progression (Bonnal, Vigevani, and Valcarcel 2012).

c Efforts to develop Ras-targeting therapies are in progress and are hoped to be useful in hematologic malignancies (Ward, Braun, and Shannon 2012).

Contributors: Stephen A. Strickland, M.D., MSCI, Annette S. Kim, M.D., Ph.D.

Suggested Citation: Strickland, S., A. Kim. 2015. TET2 Mutations in Myelodysplastic Syndromes. My Cancer Genome https://www.padiracinnovation.org/content/disease/myelodysplastic-syndromes/tet2/330/ (Updated October 16).

Last Updated: October 16, 2015

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