ETV6

Overview

ETV6 is one of a number of genes affected by aberrant somatic hypermutation in B-cell lymphomas, which complicates the interpretation of mutations at this locus. The prevalence of mutations in DLBCL has varied across different studies and may occur in as many as 10% of patients. This gene has some recurrent sites of mutations (hot spots) including multiple mutations predicted to affect splicing of ETV6 pre-mRNA. The mutation pattern in DLBCL mplies the preferential accumulation of inactivating mutations. Coding and non-coding mutations in this gene are associated with the MCD genetic subgroup of DLBCL.

History

%%{init: { 'logLevel': 'debug', 'theme': 'dark' } }%% timeline title Publication timing 2012-03-06 : Lohr : DLBCL 2017-05-01 : Albuquerque : DLBCL 2017-10-10 : Reddy : DLBCL 2018-04-12 : Schmitz : DLBCL 2018-05-01 : Chapuy : DLBCL 2018-10-01 : Arthur : DLBCL

Relevance tier by entity

Entity	Tier	Description
	1-a	aSHM target and high-confidence DLBCL gene^{1,lohrDiscoveryPrioritizationSomatic2012a?,albuquerqueEnhancingKnowledgeDiscovery2017a?}

Mutation incidence in large patient cohorts (GAMBL reanalysis)

Entity	source	frequency (%)
DLBCL	GAMBL genomes	4.97
DLBCL	Schmitz cohort	10.43
DLBCL	Reddy cohort	5.81
DLBCL	Chapuy cohort	10.26

Mutation pattern and selective pressure estimates

Entity	aSHM	Significant selection	dN/dS (missense)	dN/dS (nonsense)
BL	Yes	No	1.527	0.000
DLBCL	Yes	Yes	2.366	28.723
FL	Yes	No	2.772	0.000

aSHM regions

chr_name	hg19_start	hg19_end	region	regulatory_comment
chr12	11796001	11812968	TSS	strong_enhancer

ETV6 Hotspots

Chromosome	Coordinate (hg19)	ref>alt	HGVSp
chr12	11803078	C>T	A6V
chr12	11803087	G>A	S9N
chr12	11803094	G>A	K11=

View coding variants in ProteinPaint hg19 or hg38

View all variants in GenomePaint hg19 or hg38

ETV6 Expression

References

Reddy A, Zhang J, Davis NS, Moffitt AB, Love CL, Waldrop A, Leppa S, Pasanen A, Meriranta L, Karjalainen-Lindsberg ML, Nørgaard P, Pedersen M, Gang AO, Høgdall E, Heavican TB, Lone W, Iqbal J, Qin Q, Li G, Kim SY, Healy J, Richards KL, Fedoriw Y, Bernal-Mizrachi L, Koff JL, Staton AD, Flowers CR, Paltiel O, Goldschmidt N, Calaminici M, Clear A, Gribben J, Nguyen E, Czader MB, Ondrejka SL, Collie A, Hsi ED, Tse E, Au-Yeung RKH, Kwong YL, Srivastava G, Choi WWL, Evens AM, Pilichowska M, Sengar M, Reddy N, Li S, Chadburn A, Gordon LI, Jaffe ES, Levy S, Rempel R, Tzeng T, Happ LE, Dave T, Rajagopalan D, Datta J, Dunson DB, Dave SS. Genetic and Functional Drivers of Diffuse Large B Cell Lymphoma. Cell. 2017 Oct;171(2):481–494.e15. PMCID: PMC5659841