Table of Contents

Overview

P2RY8 encodes a G protein–coupled receptor that is expressed on germinal center B cells. Signals through this receptor promote confinement of B cells to the GC niche.1 Downstream signaling through Galpha13 (encoded by GNA13) and S1PR2 is distrupted by mutations of one of these genes in GC lymphomas including the GCB subgroup of DLBCL and BL.1

Experimental Evidence

Driver mutations affecting this gene in BL/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 80 0.0735 [0.058,0.089]
DLBCL GAMBL with Reddy 2,088 80 0.0383 [0.0301,0.0465]
DLBCL BC 231 18 0.0779 [0.0434,0.1125]
DLBCL Dana-Farber 303 23 0.0759 [0.0461,0.1057]
DLBCL NCI 470 34 0.0723 [0.0489,0.0958]
DLBCL Reddy 999 0 0.0001 [0,7e-04]
DLBCL DLBCL_ICGC 85 5 0.0588 [0.0088,0.1088]

BL

pathology Collection N mutated Incidence CI
BL GAMBL without Panea 309 28 0.0686 [0.0408,0.0965]
BL GAMBL without ICGC/Zhou 320 25 0.0033 [0,0.0094]
BL GAMBL with Panea 410 28 0.0041 [0,0.0101]
BL BLGSP 219 25 0.1142 [0.072,0.1563]
BL Zhou/ICGC 90 3 0.0333 [0,0.0704]
BL Panea 101 0 0.0010 [0,0.0071]

Mutation pattern and selective pressure estimates

Entity Missense dN/dS Nonsense dN/dS Q value
BL 35.1370 55.5821 0
FL 4.8626 13.3527 1
DLBCL 9.0075 11.6570 0

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Expression

History

%%{init: { 'logLevel': 'debug', 'theme': 'dark' } }%% timeline title Publication timing 2012-03-06 : Lohr : DLBCL 2014-12-11 : Muppidi : BL

References

1.
Muppidi J, Schmitz R, Green JA, Green JA, Xiao W, Larsen AB, Braun S, An J, Xu Y, Rosenwald A, Ott G, Gascoyne R, Rimsza L, Campo E, Jaffe E, Delabie J, Smeland E, Braziel R, Tubbs R, Cook J, Weisenburger D, Chan W, Vaidehi N, Staudt L, Cyster J. Loss of signaling via Gα13 in germinal center B cell-derived lymphoma. Nature. 2014;516:254–258.
2.
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

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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