SETD2

Overview

SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) is the primary enzyme responsible for trimethylation of histone H3 at lysine 36 (H3K36me3), a mark associated with transcription elongation and DNA mismatch repair. Loss-of-function mutations in SETD2 are found across multiple cancer types and are associated with genomic instability and poor clinical outcomes. In pheochromocytoma/paraganglioma, somatic SETD2 mutation was identified as a poor-outcome marker.

Alterations observed in the corpus

  • Somatic mutation identified in the TCGA PCC/PGL cohort (pcpg_tcga_pub, n=173) as part of a cancer-relevant gene scan; SETD2 somatic mutation was a statistically significant marker of poor outcome (worse ADFS and MFS). PMID:28162975
  • Listed among the somatic events associated with worse aggressive-disease-free survival (ADFS) and metastatic-free survival (MFS), alongside MAML3 fusion and ATRX somatic mutation. PMID:28162975
  • Chromatin modifier SETD2 enriched in the unknown mitogenic driver (UMD) subset of metastatic LUAD (especially never/former-light smokers) in a prospective MSK-IMPACT cohort of 860 patients PMID:28336552.
  • E282Rfs*9 frameshift mutation observed in 1/19 sequenced oligodendroglioma tumors PMID:28472509
  • Identified as a significantly mutated gene (SMG) in kidney renal clear cell carcinoma (KIRC), called by both MutSig2CV and MuSiC2 on the TCGA MC3 open-access MAF PMID:29596782

Cancer types (linked)

  • PHC / PGNG: Somatic SETD2 mutation is a poor-prognosis marker; enriched in tumors with more aggressive clinical behavior. PMID:28162975

Co-occurrence and mutual exclusivity

  • No specific co-occurrence patterns reported in the corpus beyond its presence in PCC/PGL tumors with high somatic mutation burden.

Therapeutic relevance

  • No direct targeted therapy for SETD2-mutant PCC/PGL described in the corpus.

Open questions

  • The mechanism by which somatic SETD2 loss promotes aggressive behavior in PCC/PGL (e.g., through H3K36me3 loss or DNA repair defects) is not characterized in the source paper. PMID:28162975

Sources

This page was processed by entity-page-writer on 2026-05-15. - PMID:28336552

This page was processed by wiki-cli on 2026-05-14. - PMID:28472509

This page was processed by wiki-cli on 2026-05-15. - PMID:29596782

This page was processed by wiki-cli on 2026-05-15.