Table 2.

H2A and H3 families of histone variants implicated in human cancer

Variant	Cancer type	Dysfunction	Proposed mechanism in promoting cancer	References
H2A.Z (H2A.Z.1)	Colorectal cancer	Overexpression	N.D.	[82]
	Undifferentiated cancers	Overexpression	N.D.	[83]
	Metastatic breast carcinoma	Overexpression	N.D.	[84]
	Primary breast cancer	Overexpression	ER alpha- and Myc-dependent upregulation	[8]
	Breast cancer (MCF7 cell line)	Overexpression	Increased proliferation	[14]
	Breast cancer	Overexpression	H2A.Z recruited at promoters of ERalpha target genes	[17]
	Melanoma	Overexpression	N.D.	[12]
	Prostate cancer (LNCaP cell line)	Overexpression	Myc-mediated H2AFZ upregulation	[91]
	Prostate cancer (LNCap xenograft)	N.D.	H2A.Zub evicted from PSA promoter/enhancer upon activation	[90]
	Prostate cancer (LNCaP cell line)	N.D.	H2A.Zac associated with oncogene activation,unmodified H2A.Z with tumor-suppressor silencing	[48]
H2A.X	B-CLL and T-PLL	Translocations and deletions chr 11q23	Increased genome instability	[130–132]
	Head and neck squamous cell carcinoma	Gene deletion	Increased genome instability	[133]
	Non-Hodgkin lymphoma	Gene mutation	Increased genome instability	[135]
	Gastrointestinal stromal tumor	Upregulation	Promote apoptosis upon the treatment with a kinase inhibitor	[138]
	Breast cancer	Gene deletion	Increased genome instability	[134]
mH2A.1	Lung cancer	Reduced protein levels/splicing defects	Suppression of cell proliferation via reduced PARP-1	[10, 13]
	Breast cancer	Reduced protein levels/splicing defects	N.D.	[10, 13]
	Melanoma	Transcriptional downregulation	Upregulation of CDK8	[12]
	Testicular, bladder, ovarian, cervical, endometrial cancers	Splicing defects	N.D.	[13]
	Colon cancer	Reduced protein levels and splicing defects	N.D.	[9, 13]
mH2A.2	Lung	Reduced protein levels	N.D.	[10]
	Breast	Reduced protein levels	N.D.	[10]
	Melanoma	Transcriptional downregulation	Upregulation of CDK8	[12]
CENP-A	Colorectal cancer	Overexpression	Aneuploidy	[222]
	Invasive testicular germ cell tumors	Overexpression	N.D.	[224]
	HCC	Overexpression	Deregulation of cell cycle and apoptotic genes	[226]
	Breast cancer	Overexpression	N.D.	[225]
	Lung adenocarcinoma	Overexpression	N.D.	[223]
H3.3	Carcinoma of the esophagus	Overexpression	N.D.	[262]
	GBM	Mutation (K27M, G34V/R)	N.D.	[15]
	Pediatric DIPG	Mutation (K27M, G34V/R)	Inhibition of EZH2 activity, reduced H3K27me3	[16, 263]