Table of Contents

Experimental Evidence

In DLBCL, mutations at the canonical hotspot (E571) have been experimentally demonstrated to cause a new function (NEO).1

Clinical Relevance

Selinexor (XPOVIO), an inhibitor of the nuclear export activity of XPO1 protein, has received FDA approval for adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy..

Relevance tier by entity

Entity Tier Description
DLBCL 1 High-confidence DLBCL 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 25 0.0230 [0.0141,0.0319]
DLBCL GAMBL with Reddy 2,088 39 0.0187 [0.0129,0.0245]
DLBCL BC 231 4 0.0173 [5e-04,0.0341]
DLBCL Dana-Farber 303 5 0.0165 [0.0022,0.0308]
DLBCL NCI 470 11 0.0234 [0.0097,0.0371]
DLBCL Reddy 999 14 0.0140 [0.0067,0.0213]
DLBCL DLBCL_ICGC 85 5 0.0588 [0.0088,0.1088]

Mutation pattern and selective pressure estimates

Entity Missense dN/dS Nonsense dN/dS Q value
BL 1.6676 0.0000 1.0000
FL 1.0100 0.0000 1.0000
DLBCL 1.2326 0.2333 0.9986

XPO1 Hotspots

Chromosome Coordinate (hg19) ref>alt HGVSp
chr2 61719471 T>C E571G
chr2 61719472 C>T E571K
Structure with HotMAPS hotspots

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Expression

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References

1.
Miloudi H, Bohers É, Guillonneau F, Taly A, Gibouin VC, Viailly PJ, Jego G, Grumolato L, Jardin F, Sola B. XPO1E571K Mutation Modifies Exportin 1 Localisation and Interactome in B-cell Lymphoma. Cancers (Basel). 2020 Sep 30;12(10):2829. PMCID: PMC7600770
2.
Jardin F, Pujals A, Pelletier L, Bohers E, Camus V, Mareschal S, Dubois S, Sola B, Ochmann M, Lemonnier F, Viailly PJ, Bertrand P, Maingonnat C, Traverse-Glehen A, Gaulard P, Damotte D, Delarue R, Haioun C, Argueta C, Landesman Y, Salles G, Jais JP, Figeac M, Copie-Bergman C, Molina TJ, Picquenot JM, Cornic M, Fest T, Milpied N, Lemasle E, Stamatoullas A, Moeller P, Dyer MJS, Sundstrom C, Bastard C, Tilly H, Leroy K. Recurrent mutations of the exportin 1 gene (XPO1) and their impact on selective inhibitor of nuclear export compounds sensitivity in primary mediastinal B-cell lymphoma. Am J Hematol. 2016 Sep;91(9):923–930.
3.
Mareschal S, Dubois S, Viailly PJ, Bertrand P, Bohers E, Maingonnat C, Jaïs JP, Tesson B, Ruminy P, Peyrouze P, Copie-Bergman C, Fest T, Jo Molina T, Haioun C, Salles G, Tilly H, Lecroq T, Leroy K, Jardin F. Whole exome sequencing of relapsed/refractory patients expands the repertoire of somatic mutations in diffuse large B-cell lymphoma. Genes Chromosomes Cancer. 2016 Mar;55(3):251–267.
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

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