XPO1

Table of Contents

Experimental Evidence
Clinical Relevance
Relevance tier by entity
Mutation incidence in large patient cohorts (GAMBL reanalysis)
- DLBCL
Mutation pattern and selective pressure estimates
XPO1 Hotspots
Expression
References

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.. Importantly, eligibility does not depend on the presence of mutations in XPO1.

Relevance tier by entity

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

Mutation incidence in large patient cohorts (GAMBL reanalysis)

DLBCL

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Mutation pattern and selective pressure estimates

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XPO1 Hotspots

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

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Expression

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References

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

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.

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.

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