Table of Contents

Overview

Mutations in the EEF1A1 gene, which encodes the eukaryotic translation elongation factor 1A1, have been reported in PMBL by Reichel et al, DLBCL by Chapuy et al and FL by Hubschmann et al.1–3 This gene has some recurrent sites of mutations (hot spots). The mutation pattern in DLBCL and FL implies the preferential accumulation of inactivating mutations. Paradoxically, one study showed that EEF1A1 knock down reduced proliferation in vitro and in xenograft experiments.1

Relevance tier by entity

Entity Tier Description
DLBCL 1 High-confidence DLBCL gene
FL 1 High-confidence FL gene
PMBL 1 High-confidence PMBL gene

Mutation incidence in large patient cohorts (GAMBL reanalysis)

DLBCL

Entity Collection N mutated Incidence 95% CI
DLBCL GAMBL without Reddy 1,089 39 0.0358 [0.0248,0.0468]
DLBCL GAMBL with Reddy 2,088 64 0.0307 [0.0233,0.038]
DLBCL BC 231 9 0.0390 [0.014,0.0639]
DLBCL Dana-Farber 303 12 0.0396 [0.0176,0.0616]
DLBCL NCI 470 14 0.0298 [0.0144,0.0452]
DLBCL Reddy 999 25 0.0250 [0.0153,0.0347]
DLBCL DLBCL_ICGC 85 4 0.0471 [0.002,0.0921]

FL

pathology Collection N mutated Incidence CI
FL GAMBL without Crouch 642 66 0.1028 [0.0793,0.1263]
FL GAMBL with Crouch 1,189 67 0.0563 [0.0432,0.0695]
FL BC 379 40 0.1055 [0.0746,0.1365]
FL Kalmbach 164 17 0.1037 [0.057,0.1503]
FL Crouch 547 1 0.0018 [0,0.0054]
FL FL_ICGC 99 9 0.0909 [0.0343,0.1475]

Mutation pattern and selective pressure estimates

Entity Missense dN/dS Nonsense dN/dS Q value
BL 3.4363 0.0000 1.0000
FL 17.1001 4.4874 0.0000
DLBCL 1.7990 3.9375 0.0204

EEF1A1 Hotspots

Chromosome Coordinate (hg19) ref>alt HGVSp
chr6 74229191 C>T A65T
chr6 74229191 C>G A65P
chr6 74229190 G>C A65G
chr6 74229188 C>T E66K
chr6 74229187 T>A E66V
chr6 74229179 G>C R69G
chr6 74229179 G>A R69C
chr6 74229094 T>A D97V
chr6 74229095 C>T D97N

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Expression

EEF1A1 Expression

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References

1.
Reichel J, Chadburn A, Rubinstein PG, Giulino-Roth L, Tam W, Liu Y, Gaiolla R, Eng K, Brody J, Inghirami G, Carlo-Stella C, Santoro A, Rahal D, Totonchy J, Elemento O, Cesarman E, Roshal M. Flow sorting and exome sequencing reveal the oncogenome of primary Hodgkin and Reed-Sternberg cells. Blood. 2015 Feb 12;125(7):1061–1072.
2.
Chapuy B, Stewart C, Dunford AJ, Kim J, Kamburov A, Redd RA, Lawrence MS, Roemer MGM, Li AJ, Ziepert M, Staiger AM, Wala JA, Ducar MD, Leshchiner I, Rheinbay E, Taylor-Weiner A, Coughlin CA, Hess JM, Pedamallu CS, Livitz D, Rosebrock D, Rosenberg M, Tracy AA, Horn H, van Hummelen P, Feldman AL, Link BK, Novak AJ, Cerhan JR, Habermann TM, Siebert R, Rosenwald A, Thorner AR, Meyerson ML, Golub TR, Beroukhim R, Wulf GG, Ott G, Rodig SJ, Monti S, Neuberg DS, Loeffler M, Pfreundschuh M, Trümper L, Getz G, Shipp MA. Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes. Nat Med. 2018 May;24(5):679–690. PMCID: PMC6613387
3.
Hübschmann D, Kleinheinz K, Wagener R, Bernhart SH, López C, Toprak UH, Sungalee S, Ishaque N, Kretzmer H, Kreuz M, Waszak SM, Paramasivam N, Ammerpohl O, Aukema SM, Beekman R, Bergmann AK, Bieg M, Binder H, Borkhardt A, Borst C, Brors B, Bruns P, Carrillo de Santa Pau E, Claviez A, Doose G, Haake A, Karsch D, Haas S, Hansmann ML, Hoell JI, Hovestadt V, Huang B, Hummel M, Jäger-Schmidt C, Kerssemakers JNA, Korbel JO, Kube D, Lawerenz C, Lenze D, Martens JHA, Ott G, Radlwimmer B, Reisinger E, Richter J, Rico D, Rosenstiel P, Rosenwald A, Schillhabel M, Stilgenbauer S, Stadler PF, Martín-Subero JI, Szczepanowski M, Warsow G, Weniger MA, Zapatka M, Valencia A, Stunnenberg HG, Lichter P, Möller P, Loeffler M, Eils R, Klapper W, Hoffmann S, Trümper L, ICGC MMML-Seq consortium, ICGC DE-Mining consortium, BLUEPRINT consortium, Küppers R, Schlesner M, Siebert R. Mutational mechanisms shaping the coding and noncoding genome of germinal center derived B-cell lymphomas. Leukemia. 2021 Jul;35(7):2002–2016. PMCID: PMC8257491

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