HIST1H1E

Overview

This is one of several genes that encode linker histone proteins that are recurrently mutated in DLBCL and FL.^1,2 Mutations are often found in the globular domain of the protein, which is critical for its interaction with DNA and other histone proteins.

History

Mutations in this gene were first described in DLBCL in 2013 by Morin et al.³ Mutations were subsequently reported in FL in 2017 by Krysiak et al⁴ and in BL by Grande et al.⁵

%%{init: { 'logLevel': 'debug', 'theme': 'dark' } }%% timeline title Publication timing 2013-08-15 : Morin : DLBCL 2015-02-12 : Reichel : PMBL 2017-01-26 : Krysiak : FL 2019-03-21 : Grande : BL

Relevance tier by entity

Entity	Tier	Description
	1	high-confidence PMBL/cHL/GZL gene
	1	high-confidence DLBCL gene
	1	high-confidence FL gene
	2	relevance in BL not firmly established

Mutation incidence in large patient cohorts (GAMBL reanalysis)

Entity	source	frequency (%)
BL	GAMBL genomes+capture	9.70
BL	Thomas cohort	7.60
BL	Panea cohort	19.80
DLBCL	GAMBL genomes	18.55
DLBCL	Schmitz cohort	17.87
DLBCL	Reddy cohort	14.51
DLBCL	Chapuy cohort	11.54
FL	GAMBL genomes	12.93

Mutation pattern and selective pressure estimates

Entity	aSHM	Significant selection	dN/dS (missense)	dN/dS (nonsense)
BL	No	Yes	14.203	0.000
DLBCL	No	Yes	4.446	6.437
FL	No	Yes	10.043	0.000

## HIST1H1E Hotspots

Chromosome	Coordinate (hg19)	ref>alt	HGVSp
chr6	26157090	G>T	A158S
chr6	26157096	A>C	K160Q
chr6	26157096	A>G	K160E
chr6	26157099	C>G	P161A
chr6	26157099	C>T	P161S
chr6	26157102	G>A	A162T
chr6	26157105	G>A	A163T
chr6	26157106	C>T	A163V
chr6	26157108	G>A	A164T
chr6	26157108	G>C	A164P
chr6	26157109	C>G	A164G
chr6	26157109	C>T	A164V
chr6	26157112	C>G	A165G
chr6	26157112	C>T	A165V
chr6	26157114	G>A	G166R
chr6	26157118	C>T	A167V
chr6	26157121	A>T	K168I
chr6	26157139	A>G	K174R

View coding variants in ProteinPaint hg19 or hg38

View all variants in GenomePaint hg19 or hg38

HIST1H1E Expression

References

Morin RD, Mendez-Lago M, Mungall AJ, Goya R, Mungall KL, Corbett RD, Johnson NA, Severson TM, Chiu R, Field M, Jackman S, Krzywinski M, Scott DW, Trinh DL, Tamura-Wells J, Li S, Firme MR, Rogic S, Griffith M, Chan S, Yakovenko O, Meyer IM, Zhao EY, Smailus D, Moksa M, Chittaranjan S, Rimsza L, Brooks-Wilson A, Spinelli JJ, Ben-Neriah S, Meissner B, Woolcock B, Boyle M, McDonald H, Tam A, Zhao Y, Delaney A, Zeng T, Tse K, Butterfield Y, Birol I, Holt R, Schein J, Horsman DE, Moore R, Jones SJ, Connors JM, Hirst M, Gascoyne RD, Marra MA. Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma. Nature. 2011 Jul 27;476(7360):298-303. doi: 10.1038/nature10351. PMID: 21796119; PMCID: PMC3210554.
Li H, Kaminski MS, Li Y, Yildiz M, Ouillette P, Jones S, Fox H, Jacobi K, Saiya-Cork K, Bixby D, Lebovic D, Roulston D, Shedden K, Sabel M, Marentette L, Cimmino V, Chang AE, Malek SN. Mutations in linker histone genes HIST1H1 B, C, D, and E; OCT2 (POU2F2); IRF8; and ARID1A underlying the pathogenesis of follicular lymphoma. Blood. 2014 Mar 6;123(10):1487-98. doi: 10.1182/blood-2013-05-500264. Epub 2014 Jan 16. PMID: 24435047; PMCID: PMC4729540.
Morin RD, Mungall K, Pleasance E, Mungall AJ, Goya R, Huff RD, Scott DW, Ding J, Roth A, Chiu R, Corbett RD, Chan FC, Mendez-Lago M, Trinh DL, Bolger-Munro M, Taylor G, Hadj Khodabakhshi A, Ben-Neriah S, Pon J, Meissner B, Woolcock B, Farnoud N, Rogic S, Lim EL, Johnson NA, Shah S, Jones S, Steidl C, Holt R, Birol I, Moore R, Connors JM, Gascoyne RD, Marra MA. Mutational and structural analysis of diffuse large B-cell lymphoma using whole-genome sequencing. Blood. 2013 Aug 15;122(7):1256–1265. PMCID: PMC3744992
Krysiak K, Gomez F, White BS, Matlock M, Miller CA, Trani L, Fronick CC, Fulton RS, Kreisel F, Cashen AF, Carson KR, Berrien-Elliott MM, Bartlett NL, Griffith M, Griffith OL, Fehniger TA. Recurrent somatic mutations affecting B-cell receptor signaling pathway genes in follicular lymphoma. Blood. 2017 Jan 26;129(4):473–483. PMCID: PMC5270390
Grande BM, Gerhard DS, Jiang A, Griner NB, Abramson JS, Alexander TB, Allen H, Ayers LW, Bethony JM, Bhatia K, Bowen J, Casper C, Choi JK, Culibrk L, Davidsen TM, Dyer MA, Gastier-Foster JM, Gesuwan P, Greiner TC, Gross TG, Hanf B, Harris NL, He Y, Irvin JD, Jaffe ES, Jones SJM, Kerchan P, Knoetze N, Leal FE, Lichtenberg TM, Ma Y, Martin JP, Martin MR, Mbulaiteye SM, Mullighan CG, Mungall AJ, Namirembe C, Novik K, Noy A, Ogwang MD, Omoding A, Orem J, Reynolds SJ, Rushton CK, Sandlund JT, Schmitz R, Taylor C, Wilson WH, Wright GW, Zhao EY, Marra MA, Morin RD, Staudt LM. Genome-wide discovery of somatic coding and noncoding mutations in pediatric endemic and sporadic Burkitt lymphoma. Blood. 2019 Mar 21;133(12):1313–1324.