Overview

ETS1 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. This gene has some recurrent sites of mutations (hot spots). The mutation pattern in DLBCL implies the preferential accumulation of inactivating mutations.

Relevance tier by entity

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Warnings

The variants reported in this gene in BL failed QC

Mutation incidence in large patient cohorts (GAMBL reanalysis)

DLBCL

Entity Collection N mutated Incidence 95% CI
DLBCL GAMBL without Reddy 1,089 67 0.0615 [0.0473,0.0758]
DLBCL GAMBL with Reddy 2,088 111 0.0532 [0.0435,0.0628]
DLBCL BC 231 11 0.0476 [0.0202,0.0751]
DLBCL Dana-Farber 303 15 0.0495 [0.0251,0.0739]
DLBCL NCI 470 37 0.0787 [0.0544,0.1031]
DLBCL Reddy 999 44 0.0440 [0.0313,0.0568]
DLBCL DLBCL_ICGC 85 4 0.0471 [0.002,0.0921]

FL

pathology Collection N mutated Incidence CI
FL GAMBL without Crouch 642 22 0.0343 [0.0202,0.0483]
FL GAMBL with Crouch 1,189 22 0.0185 [0.0108,0.0262]
FL BC 379 12 0.0317 [0.014,0.0493]
FL Kalmbach 164 6 0.0366 [0.0079,0.0653]
FL Crouch 547 0 0.0002 [0,0.0013]
FL FL_ICGC 99 4 0.0404 [0.0016,0.0792]

Mutation pattern and selective pressure estimates

Entity Missense dN/dS Nonsense dN/dS Q value
BL 16.2349 45.0315 0
FL 3.7007 33.6400 0
DLBCL 2.3729 5.1884 0

aSHM regions

chr_name hg19_start hg19_end region regulatory_comment
chr11 128339774 128345731 intron enhancer
chr11 128388492 128394163 TSS-2 active_promoter

ETS1 Hotspots

Chromosome Coordinate (hg19) ref>alt HGVSp
chr11 128391889 T>A M1?
chr11 128391888 A>C M1?
chr11 128391871 G>A L7F
chr11 128391867 T>C K8R
chr11 128391865 GC>CT P9A
chr11 128391865 G>C P9A
chr11 128391865 G>A P9S
chr11 128391861 G>A T10I
chr11 128391859 G>C L11V
chr11 128391855 G>C T12S
chr11 128391855 G>A T12I
chr11 128391853 T>C I13V
chr11 128391853 T>A I13F
chr11 128391848 G>C I14M
chr11 128391846 T>C K15R
chr11 128391841 C>G E17Q
chr11 128391841 C>A E17*
chr11 128391824 C>G E22D
chr11 128391823 G>A L23F

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Expression

Representative Mutations

BL1

Rating ★ ☆ ☆ ☆ ☆

Rating ★ ☆ ☆ ☆ ☆

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References

1.
Panea R, Love C, Shingleton JR, Reddy A, Bailey J, Moormann A, Otieno J, Ong’echa J, Oduor C, Schroêder K, Masalu N, Chao N, Agajanian M, Major M, Fedoriw Y, Richards K, Rymkiewicz G, Miles R, Alobeid B, Bhagat G, Flowers C, Ondrejka S, Hsi E, Choi W, Au-Yeung R, Hartmann W, Lenz G, Meyerson H, Lin YY, Zhuang Y, Luftig M, Waldrop A, Dave T, Thakkar D, Sahay H, Li G, Palus B, Seshadri V, Kim S, Gascoyne R, Levy S, Mukhopadhyay M, Dunson D, Dave S. The whole genome landscape of Burkitt lymphoma subtypes. Blood. 2019;
2.
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 SJM, 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. PMCID: PMC3210554