Table of Contents

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.

Experimental Evidence

Driver mutations affecting this gene in DLBCL have been experimentally demonstrated to cause a reduction or loss of function (LOF).1

Relevance tier by entity

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Mutation incidence in large patient cohorts (GAMBL reanalysis)

DLBCL

Entity Collection N mutated Incidence 95% CI
DLBCL GAMBL without Reddy 1,089 91 0.0836 [0.0671,0.1]
DLBCL GAMBL with Reddy 2,088 149 0.0714 [0.0603,0.0824]
DLBCL BC 231 15 0.0649 [0.0332,0.0967]
DLBCL Dana-Farber 303 26 0.0858 [0.0543,0.1173]
DLBCL NCI 470 49 0.1043 [0.0766,0.1319]
DLBCL Reddy 999 58 0.0581 [0.0436,0.0726]
DLBCL DLBCL_ICGC 85 1 0.0118 [0,0.0347]

Mutation pattern and selective pressure estimates

Entity Missense dN/dS Nonsense dN/dS Q value
BL 1.3788 0.0000 1
FL 2.6609 18.3470 1
DLBCL 0.8997 7.0517 0

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=

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Expression

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References

1.
Wang Q, Dong S, Yao H, Wen L, Qiu H, Qin L, Ma L, Chen S. ETV6 mutation in a cohort of 970 patients with hematologic malignancies. Haematologica. 2014 Oct;99(10):e176–178. PMCID: PMC4181263
2.
Albuquerque MA, Grande BM, Ritch EJ, Pararajalingam P, Jessa S, Krzywinski M, Grewal JK, Shah SP, Boutros PC, Morin RD. Enhancing knowledge discovery from cancer genomics data with Galaxy. Gigascience. 2017 May 1;6(5):1–13. PMCID: PMC5437943
3.
Lohr JG, Stojanov P, Lawrence MS, Auclair D, Chapuy B, Sougnez C, Cruz-Gordillo P, Knoechel B, Asmann YW, Slager SL, Novak AJ, Dogan A, Ansell SM, Link BK, Zou L, Gould J, Saksena G, Stransky N, Rangel-Escareño C, Fernandez-Lopez JC, Hidalgo-Miranda A, Melendez-Zajgla J, Hernández-Lemus E, Schwarz-Cruz y Celis A, Imaz-Rosshandler I, Ojesina AI, Jung J, Pedamallu CS, Lander ES, Habermann TM, Cerhan JR, Shipp MA, Getz G, Golub TR. Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing. Proc Natl Acad Sci U S A. 2012 Mar 6;109(10):3879–3884. PMCID: PMC3309757
4.
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

Citing

If you use the information or data from this site, please cite

Krysta Coyle, Kostiantyn Dreval, Daniel Hodson and Ryan D. Morin. Audit of B-cell cancer genes. Blood Adv (2025) 9 (8): 2019–2031.

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