Table 2.

The function of H2A variants in cancer.

Histone	Cancer Type	Alteration	Observation/Function	PTM Involvement	References
H2A.Z	Breast	Upregulation	Correlates with poor survival, promotes proliferation, involved in gene activation by estrogen signalling	Dimethylation on K101 promotes proliferation by activating cyclinA1 H2A.Z acetylation may be responsible for increased p21 expression in ER-negative p53−/− breast cancer cells	[34,92,134,135,136]
	Prostate	Upregulation	Involved in gene activation by androgen signalling, poises PSA activation	Acetylation and deubiquitination are necessary for oncogenic hormone-mediated activation	[32,137,138,139,140]
	Bladder	Upregulation	Promotes cell proliferation and oncogene transcription by recruiting WDR5 (MLL complex) and BPTF (NuRD complex)	Unknown	[141]
H2A.Z.1	Hepatocellular carcinoma	Upregulation	Correlates with poor survival, promotes tumour growth and EMT	Unknown	[142]
H2A.Z.2	Melanoma	Upregulation	Correlates with poor survival, its depletion sensitizes cells to chemotherapy	Unknown	[143,144]
macroH2A1, macroH2A2	Melanoma	Downregulation	Promotes disease progression and metastasis	Unknown	[145,146,147]
macroH2A1, macroH2A2	Bladder cancer	Downregulation	Correlates with disease progression, promotes cell growth, stemness and invasiveness	Unknown	[148,149]
macroH2A1	Hepatocellular carcinoma	Upregulation	Higher immunopositivity in steatosis-associated hepatocellular carcinoma, prevents chemotherapy-induced senescence	Unknown	[150,151]
macroH2A1.1, macroH2A1.2	Breast cancer	Increased macroH2A1.2/macroH2A1.1 ratio	Observed in highly proliferative tumours, correlates with poor survival, promotes tumour growth and metastasis	Unknown	[152]
macroH2A1.1	Colorectal cancer	Downregulation	Correlates with poor survival, promotes proliferation and metastasis	Unknown	[112]
macroH2A1.1	Lung cancer	Downregulation	Correlates with higher risk of tumour recurrence	Unknown	[153,154]
macroH2A2	Anal neoplasm	Downregulation	Correlates with disease progression	Unknown	[155]
H2A.X	Sporadic breast cancer	Deletion	Proposed to increase genomic instability and tumorigenesis as observed in KO mice	Does not apply	[118,119,156,157]
	Neuroblastoma	Deletion	Correlates with disease progression and poor prognosis	Does not apply	[158,159]
	Head and neck squamous cell carcinoma	Deletion	Associated with higher genomic instability and reduced radiosensitivity, included in predictive model for recurrence and metastasis risk	Does not apply	[160,161,162]
	Chronic lymphocytic leukaemia	Deletion	Associated with higher genomic instability, correlates with poor prognosis	Does not apply	[163,164]
	Triple negative breast cancer	Upregulation	High levels of γ-H2A.X correlate with poor prognosis	S139 Phosphorylation	[165]
	Melanoma	Upregulation	High levels of γ-H2A.X observed in melanocytic lesions	S139 Phosphorylation	[166,167]
	Breast cancer	Downregulation	Correlates with better prognosis	Chemotherapy induces H2A.X degradation mediated by polyubiquitination at K13 and K15	[168]
	Colon cancer cells	Downregulation	Promotes EMT	Unknown	[169]
	Breast cancer cells	Downregulation	Promotes EMT	Unknown	[170]