Table 1.

Major classes of histone mutations in cancer

Histone	Aberration	Proximal mechanism*	Cancer type	References
H3	K27M	Strong inhibition of PRC2 methyltransferase activity in trans	Pediatric midline gliomas, AML (infrequent)	(9–11,16,18)
	K36M	Strong inhibition of H3 K36-specific methyltransferases in trans	Chondroblastoma, undifferentiated sarcoma, chondrosarcoma, head and neck squamous cell carcinoma (subset)	(12,17,19)
H3.3	G34R/V/W/L	Inhibition of H3 K36-specific methyltransferases in cis	Pediatric glioma (predominantly R/V), osteosarcoma, giant cell tumor of the bone (predominantly W/L)	(12,20,21)
H3	Diverse missense	Unknown, possibly nucleosome destabilization	Many cancers	(14,15,22)
H4	Diverse missense	Unknown, possibly nucleosome destabilization	Many cancers	(15,22)
H4G	Overexpression	Unknown	Breast cancer	(23)
H2A	Diverse missense	Unknown, possibly nucleosome destabilization	Many cancers, including diffuse large B-cell lymphoma (C4)	(15,22,58)
H2A.B	Overexpression	Incorporation may result in nucleosome destabilization	Many cancers, high rate in diffuse large B-cell lymphoma	(78)
H2B	E76K and other globular domain missense	Likely nucleosome destabilization	Many cancers, including diffuse large B-cell lymphoma (C4)	(13–15,58)
H1B, H1C, H1D, H1E	Diverse missense	Loss of nucleosome association and/or reduced capacity for chromatin compaction	Diffuse large B-cell lymphoma, Hodgkin lymphoma, follicular lymphoma	(24–27,58)
H1B	Increased expression	Unclear, may be a marker of proliferative activity	Neuroendocrine tumors and prostate cancer	(59,60)
H1.X	Increased expression	Unclear, may be a marker of proliferative activity	Neuroendocrine tumors	(61)
H1.0	loss/reduced expression	Chromatin decompaction, increased self-renewal and tumor heterogeneity	Many cancers, including glioblastoma and breast cancer	(62)
	Increased expression	Unknown	Lung squamous cell carcinoma (subset)	(120)

^*Simplified, refer to cited works for detailed discussion