Table 1.

Alterations of KMTs and KDMs in cancer

Enzymes	Genetic Alteration	Substrates	Function	Cancer
KMT2C MLL3	Mutations and deletion [93, 100, 101]	H3K4me1, me2, and me3	A co-activator complex of nuclear receptors	Medulloblastoma, Opisthorchis viverrini– related cholangio-carcinoma, acute myeloid leukemia, glioblastoma, melanoma, and colorectal, pancreatic, lung, bladder and breast cancers [93, 100, 101].
KMT2D MLL2	Recurrent mutations, duplications and trans- locations [93, 95, 98–100]	H3K4me3	A coactivator for Estrogen Receptor (ER) α [195]	Medulloblastoma, non-Hodgkin lymphoma, multiple myeloma, renal cell carcinoma, lung cancer, prostate cancer [93, 95, 98–100]
KMT3A SETD2	truncating or missense mutations [94, 103–106]	H3K36me3	Transcription activation, and binds to the promoters of adenovirus 12 E1A gene	Early T-cell precursor acute lymphoblastic leukaemia, clear cell renal carcinoma [94, 103–106]
KMT3B NSD1	Mutations, fuse to NUP98, microdeletion, and minimal common regions of gain [107]	H3K36me1, me2, and me3	Transcriptional intermediary factor	Carcinoma of the upper aero-digestive tract, acute myeloid leukemia, ganglioglioma, lung adenocarcinoma in never smokers, acute lymphoblastic leukemia, neuroblastoma, and Wilms tumor [107].
KMT6A EZH2	Mutations and overexpression [74–90]	H3K27me1, me2, and me3	Repressing expression of HOXC8, HOXA9, MYT1, CDKN2A and retinoic acid target genes	A wide variety of cancers [74–90]
KMT8 PRDM2 /RIZ1	Inactivating mutation and deletion, silencing [194–197]	H3K9me3	An ER co-activator [198	hepatocellular carcinoma, oral squamous cell carcinomas, prostate cancer, breast cancer cells [194–197]
KDM3B JMJD1B	cryptic deletion or over- expression[105]	H3K9me1 and me2	Synergistic interaction with CBP, inducing leukemogenic oncogene lmo2 expression [199]	myeloid malignancies, prostate cancer [105, 199]
KDM5C JARID1C	inactivating mutations [94]	H3K4me3	Transcriptional repression of neuronal genes	clear cell renal carcinoma [94]
KDM6A UTX	Inactivating mutations [78, 91–95]	H3K27 me2, and me3	HOX expression, recruitment of the PRC1 complex and monoubiquitination of histone H2A	Squamous cell carcinomas, acute myeloid leukemias (AML), glioblastoma, breast, bladder and colorectal cancers [78, 91–95]
KMT2A MLL1	Translocation, overexpression [110–112, 117]	H3K4me1	HOX and E2F3-dependent gene expression	Breast cancer cells, prostate cancer, and glioblastoma multiforme [110–112, 117]
NSD3 WHSC1L1	Translocation, amplification [114, 201]	H3K36 me1 and me2	Gene expression in cell growth, motility, cell cycle, and apoptosis [202]	Leukemia, pancreatic ductal adenocarcinoma, breast and lung cancers [114, 201, 202]
NSD2 WHSC1 MMSET	Translocation, overexpression [115,116]	H3K36me1and me2	Interact with β-catenin [203]	multiple myeloma, bladder cancer neuroblastoma [115,116]
KMT1C G9a	Over expression [126]	H3K9me1 and me2, H3K27me	DNA methylation, gene expression silence, and cell cycle [126, 214, 215]	Hepatocellular carcinoma [126]
KMT1E SETDB1	Amplification [127]	H3K9me3	Silencing of euchromatic genes and interaction with DNMT3A [212]	Melanoma [127]
KMT2E MLL5	Over expression [216]	H3K4me and me2	A coactivator of RAR-alpha and cell cycle regulator	AML, HPV16/18-associated cervical cancers [204, 205]
KMT3C SMYD2	Over expression [123]	H3K4me H3K36me2	Rb and p53 methylation and cell cycle [121, 122]	esophageal squamous cell carcinoma [123]
KMT3E SMYD3	Over expression [118–120]	H3K4me2 and me3, H4K5me, H4K20me	MMP9 expression [217]	colorectal carcinoma, hepatocellular carcinoma, and breast cancer [118–120]
KDM1A LSD1	Over expression [131–134]	H3K4me and me2, H3K9me	A coactivator of androgen receptor and snail/slug [133, 218]	Bladder, prostate, lung and colorectal cancer [131–134]
KDM3A JMJD1A	Over expression [207, 208]	H3K9me1 and me2	HOXA1 and CCND1 expression and G1S transition [207, 208]	Bladder and lung cancers [207, 208]
KDM5A JARID1A	Overexpressed and gene fusion [219–221]	H3K4me2 and me3	Transcription of HOX and repression of CXCL12 genes [143]	Gastric cancer, leukemia and cervical cancer [219–219]
KDM2B FBXL10	Down-regulation [211]	H3K36me2 H3K4me3	Binds the transcribed region of ribosomal RNA and represses the transcription of ribosomal RNA [149].	A hotspot for proviral insertion in murine tumors, Human brain tumors [211].
KDM4B JMJD2B	Over expression [209, 210]	H3K9me2 and me3	A co-factor of estrogen receptor [223]	Bladder, lung and gastric cancer [209, 210]
KDM5B JARID1B	Over expression the copy number gain [144–146, 188]	H3K4 me1, me2 and me3	Growth regulation, co-regulation of the E2F/RB1, BRCA1 and HOXA5 [223]	Bladder, prostate, breast cancer melanoma, lung cancer [144–146, 188]
KDM6B JMJD3	Overexpression [148]	H3K9 and H3K36	HOX gene expression and inflammatory response [150, 224]	Prostate cancer [148]