Appendix C.

Selected histone methyltransferases in cancer

Name	Synonyms	Histone target(s)	Links to cancer
KMT1A	SUV39H1	H3K9	Overexpressed in colorectal cancer (Kang et al. 2007), associated with transcriptional repression
KMT1C	G9a, EHMT2	H3K9	Overexpressed in lung cancers (Watanabe et al. 2008; Chen et al. 2010, for advanced lung cancer), regulation of centrosome duplication via chromatin structure (Kondo et al. 2008)
KMT1F	SETDB2	H3K9	Involved in chromosome segregation (Falandry et al. 2010)
KMT2A	MLL	H3K4	Rearranged and translocated in leukemias (Zhang et al. 2012a)
KMT2B	MLL2	H3K4	Frequently mutated in non-Hodgkin lymphoma (Morin et al. 2011), critical role in lymphomagenesis (Chung et al. 2012), role in multiple myeloma and Kabuki syndrome
KMT2C	MLL3	H3K4	Germline mutation in colorectal cancer and AML (Li et al. 2013a); mutations in glioblastoma, melanoma, pancreatic carcinoma, and colorectal cancer
KMT2D	MLL4	H3K4	Regulates cell-cycle progression and viability in colon cancer (Ansari et al. 2012)
KMT2E	MLL5	H3K4	Implicated as a tumor suppressor, MLL5 expression positive prognostic in AML (Damm et al. 2011)
KMT3A	SETD2	H3K36	Mutations in high-grade gliomas (Fontebasso et al. 2013), tumor suppressor in breast cancer and renal cell carcinoma (Hakimi et al. 2012)
KMT3B	NSD1	H3K36	Mutated in AML, myeloma, and lung cancers, NUP98-NSD1 translocation linked to tumorogenesis in AML (Wang et al. 2007)
KMT3C	SMYD2	H3K36	Overexpression in esophageal squamous cell carcinoma correlated with poor survival (Komatsu et al. 2009)
KMT3E	SMYD3	H3K4, H4K5	Overexpressed in liver, breast, and rectal carcinomas (Van Aller et al. 2012)
KMT3F	WHSC1L1/NSD3	H3K36	Overexpressed in CML, bladder, lung, and liver cancers (Kang et al. 2013); amplified in human breast cancer cell lines (Angrand et al. 2001)
KMT3G	WHSC1/NSD2	H3K36	Implicated in constitutive NF-κB signaling for cancer cell proliferation, survival, and tumor growth (Yang et al. 2012), overexpressed in myeloma because of t(4;14) chromosomal translocation, modulates cMYC in myeloma (Min et al. 2012)
KMT4	DOT1L	H3K79	Implicated in MLL-rearranged leukemias (Krivtsov et al. 2008; Bernt and Armstrong 2011)
KMT5A	SETD8/PR-SET7	H4K20	Overexpressed in bladder cancer, NSCLC, small cell lung cancer, pancreatic cancer, hepatocellular carcinoma, and chronic myelogenous leukemia (Takawa et al. 2012)
KMT6	EZH2	H3K27	Catalytic component of PRC2 complex (Kuzmichev et al. 2002), overexpressed, is a marker for advanced and metastatic breast and prostate cancer (Chase and Cross 2011), essential for glioblastoma cancer stem-cell maintenance (Suva et al. 2009), somatic mutations in follicular and diffuse large B-cell lymphomas (Morin et al. 2010)
KMT7	SET7/SET9/SETD7	H3K4	Regulation of the estrogen receptor (Subramanian et al. 2008)
PRDM14		Unknown	Amplified and overexpressed in breast cancer (Nishikawa et al. 2007; Moelans et al. 2010), overexpressed in lymphoid neoplasms, and implicated in initiation of lymphoblastic leukemia (Dettman et al. 2011)
PRMT4	CARM1	H3R17, H3R26	Deregulated in melanoma (Limm et al. 2013), methylation CBP/P300 required for estrogen-induced targeting to chromatin (Ceschin et al. 2011)
PRMT5		H4R3, H3R8	Essential component of HIF-1 signaling (Lim et al. 2012); silences the tumor suppressor ST7 and is overexpressed in GBM (Yan et al. 2014), non-Hodgkin’s lymphoma (Chung et al. 2013), and melanoma (Nicholas et al. 2013)
PRMT6	H3R2, H3R42		Overexpressed in prostate carcinoma (Vieira et al. 2014); PRMT6 silencing reduces PELP1-mediated ER activation, proliferation, and colony formation in breast tumor cells (Mann et al. 2014)

AML, acute myelogenous leukemia; CML, chronic myelogenous leukemia; MLL, mixed lineage leukemia;

NSCLC, non-small-cell lung carcinoma; PRC2, Polycomb repressive complex 2; HIF-1, hypoxia-inducible factor 1; GBM, glioblastoma multiforme; ER, estrogen receptor.