• What is DNMT3A?
  • DNMT3A in Acute Myeloid Leukemia
  • DNMT3A c.2645G>C (R882P)
  • Clinical Trials

DNMT3A

The DNA (cytosine-5-)-methyltransferase 3 alpha (DNMT3A) gene encodes a protein involved in epigenetic gene regulation (Gene 2013; Li et al. 2007).

DNMT3A is most frequently mutated in hematologic malignancies such as acute myeloid leukemia and myelodysplastic syndromes, but it has also been observed in other cancers, including lung cancer (Kim et al. 2013).

Related Pathways

Contributors: Scott Wheeler, Ph.D. (through June 2014), Adam Seegmiller, M.D., Ph.D., Cindy L. Vnencak-Jones, Ph.D.

Suggested Citation: Wheeler, S., A. Seegmiller, C. Vnencak-Jones. 2015. DNMT3A. My Cancer Genome https://www.padiracinnovation.org/content/disease/acute-myeloid-leukemia/dnmt3a/?tab=0 (Updated December 4).

Last Updated: December 4, 2015

DNMT3A in Acute Myeloid Leukemia

DNMT3A mutations occur in 17.1% of AML (COSMIC). DNMT3A mutations most often occur at the R882 residue of the protein, and they are believed to cause loss of function (Shih et al. 2012). DNMT3A mutations fall outside the “two-hit” theory of leukemogenesis as it was originally conceived. Some have proposed categorizing DNMT3A mutations into a new class of mutations; members of the new class—class III—would be defined as mutations occurring in epigenetic modifiers (Naoe and Kiyoi 2013; Shih et al. 2012). Similar to IDH1 and IDH2 mutations, DNMT3A mutations affect DNA methylation and as such, play a role in cancer development through deregulation of gene expression.​

Contributors: Scott Wheeler, Ph.D. (through June 2014), Adam Seegmiller, M.D., Ph.D., Cindy L. Vnencak-Jones, Ph.D.

Suggested Citation: Wheeler, S., A. Seegmiller, C. Vnencak-Jones. 2013. DNMT3A in Acute Myeloid Leukemia. My Cancer Genome https://www.padiracinnovation.org/content/disease/acute-myeloid-leukemia/dnmt3a/ (Updated September 9).

Last Updated: September 9, 2013

DNMT3A c.2645G>C (R882P) Mutation in Acute Myeloid Leukemia

Properties
Location of mutation Exon 23 (Ensembl); kinase domain (UniProt)
Frequency of DNMT3A mutations in AML 17.1% (COSMIC)
Frequency of DNMT3A R882P mutation in DNMT3A-mutated AML 1.4% (COSMIC)
Implications for Targeted Therapeutics
Response to FLT3 inhibitors Unknown at this time
Response to MEK inhibitors Unknown at this time
Response to JAK2 inhibitors Unknown at this time

The R882P mutation results in an amino acid substitution at position 882 in DNMT3A, from an arginine (R) to a proline (P). The prognostic significance of this mutation is unclear (Dohner and Gaidzik 2011; Shih et al. 2012). ​

Contributors: Scott Wheeler, Ph.D. (through June 2014), Adam Seegmiller, M.D., Ph.D., Cindy L. Vnencak-Jones, Ph.D.

Suggested Citation: Wheeler, S., A. Seegmiller, C. Vnencak-Jones. 2013. DNMT3A c.2645G>C (R882P) Mutation in Acute Myeloid Leukemia. My Cancer Genome https://www.padiracinnovation.org/content/disease/acute-myeloid-leukemia/dnmt3a/294/ (Updated September 9).

Last Updated: September 9, 2013

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