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
Suggested Citation: Wheeler, S., A. Seegmiller, C. Vnencak-Jones. 2015. DNMT3A.
My Cancer Genome https://www.padiracinnovation.org/content/disease/myelodysplastic-syndromes/dnmt3a/?tab=0
(Updated December 4).
Last Updated: December 4, 2015
DNMT3A in Myelodysplastic Syndromes
DNMT3A mutations occur in 7.8% of MDS (COSMIC). DNMT3A mutations are observed in all types of MDS (Cazzola, Della Porta,
and Malcovati 2013). DNMT3A mutations most often occur at the R882 residue of the
protein in MDS (COSMIC), and they are believed to cause loss of
function (Shih et al.
2012). However, other mutations are spread throughout the gene. DNMT3A mutations
affect DNA methylation and, as such, play a role in cancer development through deregulation
of gene expression.
DNMT3A mutations have been associated with
poor outcomes in some (RCMD and RAEB) but not all types of MDS (Cazzola, Della
Porta, and Malcovati 2013; Walter et al. 2011). In addition,
Bejar et al. (2014) observed
that DNMT3A mutations predict shorter overall survival following hematopoietic stem cell
transplantation. In RARS, DNMT3A mutations often co-occur with SF3B1 mutations, and no
association between DNMT3A mutations and poor outcome is observed (Bejar et al.
Della Porta, and Malcovati 2013).
Suggested Citation: Strickland, S., A. Kim. 2014. DNMT3A in Myelodysplastic
Syndromes. My Cancer Genome https://www.padiracinnovation.org/content/disease/myelodysplastic-syndromes/dnmt3a/
(Updated September 23).
Last Updated: September 23, 2014
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