KMT2C

Overview

KMT2C (MLL3) is a histone H3K4 methyltransferase and a recurrent epigenetic-regulator driver in lymphoid malignancies.

Alterations observed in the corpus

  • Epigenetic regulator enriched in M-CLL, primarily via 7q36.1b loss (2.5%) PMID:35927489.
  • Altered in 10% of cervical cancer patients profiled at MSK (n=177); enriched in squamous cell carcinoma (14%) vs gastric-type adenocarcinoma (0%); one of the most prevalent alterations in cervical cancer alongside PIK3CA, ERBB2, and KMT2D PMID:37643132.
  • Mutated in 13% of a longitudinal African breast cancer cohort PMID:36585450
  • KMT2C is a chromatin-modifying gene with high prevalence of non-silent variants in metastatic UC (UC-GENOME cohort) PMID:36333289
  • KMT2C LOF mutations in 6% of GBC PMID:36228155
  • Somatic mutations detected in medulloblastoma WES cohort (Broad, 92 tumors) PMID:22820256
  • Significantly mutated gene in pancreatic ductal adenocarcinoma (ICGC, 142 tumors); involved in chromatin modification and transcription regulation PMID:23103869
  • Chromatin-modifying gene recurrently altered in AML; part of the epigenetic modifier category alongside EZH2, KDM6A, and KMT2A in the TCGA AML cohort PMID:23634996
  • Missense mutation in ACC; histone methyltransferase (MLL3); part of the chromatin-remodeling gene cluster recurrently mutated in ACC PMID:23685749
  • Mutated in adenoid cystic carcinoma (ACC); part of a cluster of chromatin-remodeling genes collectively mutated in 12/24 ACC cases PMID:23778141
  • Somatic mutation as part of the histone lysine methyltransferase KMT2A/KMT2C/KMT2E group, collectively altered in 16% of transitional cell carcinoma (BLCA) bladder tumors in a 99-sample WES cohort PMID:24121792
  • Mutated in 2/8 (25%) gallbladder cancer (GBC) discovery-screen tumors in a biliary tract cancer WES study; absent in intrahepatic cholangiocarcinoma (IHCH) in this cohort PMID:24185509
  • Somatic mutation in 2/23 (9%) pancreatic carcinomas with acinar differentiation (reported as MLL3) in a WES study of rare pancreatic tumor subtypes PMID:24293293
  • KMT2C (histone methyltransferase) is recurrently mutated in ESCC, contributing to epigenetic dysregulation PMID:24686850
  • KMT2C is listed among recurrently mutated genes in the HCC WES landscape (n=1,289), part of the chromatin-modifier/epigenetic regulator gene set in hepatocellular carcinoma. PMID:24798001
  • Novel somatic mutation in chromatin/methyltransferase regulators in Ewing sarcoma WGS cohort PMID:25223734
  • Mutated in 6/22 gynaecologic carcinosarcomas (27%, MLL3), mostly missense with truncations; part of the most prominently mutated chromatin-remodelling gene class PMID:25233892
  • Mutated in 38.5% of 39 aggressive cSCC tumors; strongest clinical association — bone invasion 53% vs 10% wild-type (p=0.008); HR 5.16 (95% CI 1.55-17.18) for recurrence or death (p=0.003) PMID:25303977
  • KMT2C among candidate chromatin-remodeling dark-matter drivers in PTC; 93 mutations across 57 epigenetic regulator genes in 80/402 (20.0%) tumors included KMT2C PMID:25417114
  • Chromatin-modifying gene mutated in UTUC; mutations common in both low- and high-grade tumors and concordant across spatial tumor components, suggesting early/clonal events PMID:26278805
  • Frameshift p.Thr3941fs (Sézary syndrome) and truncating p.Gly1246* (mycosis fungoides) loss-of-function mutations in CTCL PMID:26551667
  • Truncating chromatin-modifier mutations in primary prostate cancer; enriched in the 26% unclassified genomic subset with high SCNA burden PMID:26544944
  • Recurrently mutated (2 mutations in 2 tumors; MLL3) in adenoid cystic carcinoma (ACC; n=25 WGS); part of a chromatin-regulator mutation cluster including KMT2D, KDM6A, SMARCA2, and SMARCC1 PMID:26862087
  • KMT2C, together with KMT2A, KMT2D, and SETD2, are histone methyltransferases mutated collectively in 24% of ATC vs 7% of PDTC (P = 0.02) in a 341-gene panel sequencing study of thyroid cancers PMID:26878173
  • Significantly mutated methyltransferase (MLL3) in lung ADC in the TCGA pan-lung cancer cohort PMID:27158780
  • Mutated in 11.4% of breast cancers (ER+ TSG-driver); often subclonal in IntClust1, more clonal in IntClust8; associated with lower grade in a 2,433-sample targeted sequencing study PMID:27161491
  • Mutated in ~10% of unclassified renal cell carcinoma (uRCC, n=62); one of the most frequent chromatin-modulator alterations alongside KMT2D and KMT2A; KMT2A/C/D combined represent 16% of the cohort; cases cluster in the chromatin/DNA-damage regulator subgroup. PMID:27713405
  • KMT2C (MLL3) E704X nonsense mutation identified in pediatric AML as a BET-inhibitor target in comprehensive clinical genomic sequencing PMID:28007021.
  • KMT2C (MLL3) histone-modifier alterations frequent in esophageal squamous cell carcinoma (ESCC), co-altered with KMT2D and KDM6A; 3/4 ESCC3 tumors harbored KMT2D mutations PMID:28052061.
  • Chromatin modifier enriched in UMD (unmatched molecular driver) subset, especially never/former-light smokers, in prospective LUAD cohort (860 patients, MSK-IMPACT) PMID:28336552
  • Mutated in 7.9% of clear-cell endometrial carcinoma (CCEC); 3 N-terminal frameshifts plus 3 missense mutations affecting the SET methyltransferase domain; first report of KMT2C somatic mutation in CCEC PMID:28485815
  • Recurrent histone-methylation-modifier mutations across medulloblastoma subgroups PMID:28726821
  • Most frequently mutated newly recognized SMG in MIBC (18%, n=412, TCGA BLCA 2017); less frequently mutated in MSK metastatic gastroesophageal cancer vs TCGA non-MSI-H (q≤0.10). PMID:28988769
  • Significantly less frequently mutated in MSK metastatic gastroesophageal cancer (EGC) cohort vs TCGA non-MSI-H (q≤0.10), suggesting differential selection in metastatic vs localized disease. PMID:29122777
  • Epigenetic-regulator SMG significantly enriched in metastatic vs primary PRAD tumors in the 1,013-sample WES meta-cohort (prad_p1000); part of the metastasis-enrichment genomic signature proposed for risk stratification in localized prostate cancer. PMID:29610475

Cancer types (linked)

  • CLLSLL — M-CLL-enriched driver reflecting epigenetic pathway convergence in the IGHV-mutated subtype PMID:35927489.
  • CESC — altered in 10% of cervical cancers; most prevalent in squamous subtype (14%) PMID:37643132.

Co-occurrence and mutual exclusivity

Therapeutic relevance

  • None reported.

Open questions

  • None noted.

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:36585450

This page was processed by crosslinker on 2026-05-14. - PMID:36333289

This page was processed by crosslinker on 2026-05-14. - PMID:36228155

This page was processed by crosslinker on 2026-05-14. - PMID:22820256

This page was processed by crosslinker on 2026-05-14. - PMID:23103869

This page was processed by crosslinker on 2026-05-14. - PMID:23634996

This page was processed by crosslinker on 2026-05-14. - PMID:23685749

This page was processed by crosslinker on 2026-05-14. - PMID:23778141

This page was processed by crosslinker on 2026-05-14. - PMID:24121792

This page was processed by crosslinker on 2026-05-14. - PMID:24185509

This page was processed by crosslinker on 2026-05-14. - PMID:24293293

This page was processed by crosslinker on 2026-05-14. - PMID:24686850

This page was processed by crosslinker on 2026-05-14. - PMID:24798001

This page was processed by crosslinker on 2026-05-14. - PMID:25223734

This page was processed by crosslinker on 2026-05-14. - PMID:25233892

This page was processed by crosslinker on 2026-05-14. - PMID:25303977

This page was processed by crosslinker on 2026-05-14. - PMID:25417114

This page was processed by crosslinker on 2026-05-14. - PMID:26278805

This page was processed by crosslinker on 2026-05-14. - PMID:26551667

This page was processed by entity-page-writer on 2026-05-15. - PMID:26544944

This page was processed by entity-page-writer on 2026-05-15. - PMID:26862087

This page was processed by entity-page-writer on 2026-05-15. - PMID:26878173

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:27161491

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

This page was processed by entity-page-writer on 2026-05-15. - PMID:28007021

This page was processed by entity-page-writer on 2026-05-15. - PMID:28052061

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:28485815

This page was processed by entity-page-writer on 2026-05-15. - PMID:28726821

This page was processed by wiki-cli on 2026-05-15. - PMID:28988769

This page was processed by wiki-cli on 2026-05-15. - PMID:29122777

This page was processed by entity-page-writer on 2026-05-15. - PMID:29610475

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