DNMT3A

Overview

DNMT3A encodes a de novo DNA methyltransferase and is a recurrently mutated epigenetic regulator across T-cell lymphomas and myeloid malignancies.

Alterations observed in the corpus

  • Mutated in 19% (25/132) of nodal peripheral T-cell lymphomas profiled on MSK-IMPACT, making it the third-most-frequently altered gene after TET2 and RHOA PMID:37078708.
  • DNMT3A is the most prevalent clonal hematopoiesis driver in MSK patients with nonhematologic cancer; in 26 patients who developed a hematologic malignancy, DNMT3A CH VAFs largely decreased at disease onset (in contrast to JAK2/TP53 expansion) PMID:38147626.
  • HBx relocates DNMT3A to tumor suppressor gene promoters (e.g., p16/INK4A), causing regional hypermethylation in HBV-related HCC PMID:22634756
  • Among the most significantly mutated DNA-methylation genes in AML; allelic expression bias observed; co-occurs with NPM1 and FLT3; mutually exclusive with transcription-factor fusions PMID:23634996
  • Somatic variants in 13 variants across 12 patients (epigenetic regulator) in whole-exome sequencing of myeloproliferative neoplasms (ET, PV, MF) as part of the CALR discovery cohort PMID:24325359
  • Focal 2p23.3 deletion in 5/25 (20%) Sézary syndrome (2 homozygous) with concordant loss of expression, implicating DNMT3A as an epigenetic tumor suppressor in CTCL PMID:26551667
  • Mentioned in study PMID:26824661
  • Modest q-value as a significantly mutated gene in lung ADC; recurrent AKT1 p.E17K and CDK4 p.R24L mutations observed in the same cohort PMID:27158780
  • DNMT3A identified as a frequent founding-clone driver in AML (n=1,540); modifies the prognostic effect of FLT3-ITD, NRAS G12/13, IDH2 R140, and RAD21 mutations; included in the authors’ recommended prognostic panel PMID:27276561
  • Mutated in 5% of unclassified renal cell carcinoma (uRCC) cases in a 62-case MSKCC MSK-IMPACT cohort PMID:27713405
  • Frequently mutated in AML/MDS; persisted in remission in some patients after 10-day decitabine cycles, appearing in nonleukemic rising clones consistent with clonal hematopoiesis of indeterminate potential; did not predict decitabine response PMID:27959731

Cancer types (linked)

Co-occurrence and mutual exclusivity

  • Co-occurs within the TET2/RHOA/IDH2-altered TFH-phenotype PTCL landscape PMID:37078708.

Therapeutic relevance

  • No independent prognostic effect reported in the PTCL cohort treated with CHOP-based chemotherapy PMID:37078708.

Open questions

  • None flagged in the corpus.

Sources

This page was processed by crosslinker on 2026-05-09. - PMID:22634756

This page was processed by crosslinker on 2026-05-09. - PMID:23634996

This page was processed by crosslinker on 2026-05-09. - PMID:24325359

This page was processed by crosslinker on 2026-05-09. - PMID:26551667

This page was processed by entity-page-writer on 2026-05-15. - PMID:26824661

This page was processed by entity-page-writer on 2026-05-15. - PMID:27158780

This page was processed by entity-page-writer on 2026-05-15. - PMID:27276561

This page was processed by entity-page-writer on 2026-05-15. - PMID:27713405

This page was processed by wiki-cli on 2026-05-14. - PMID:27959731

This page was processed by entity-page-writer on 2026-05-15.