Table of Contents

Overview

Mutations in CARD11 were initially described as enriched in the ABC subgroup of DLBCL.1 More recent data contradicts this association and has implicated CARD11 in FL and additional B-cell lymphomas including FL and MCL.2,3

Experimental Evidence

The functional effect of CARD11 mutations in DLBCL was explored in the original study.1

Relevance tier by entity

Entity Tier Description
BL 2 Role of CARD11 mutations in BL requires confirmation
DLBCL 1 High-confidence DLBCL gene
FL 1 High-confidence FL gene
MCL 1 High-confidence MCL gene
MZL 1 High-confidence MZL gene

Mutation incidence in large patient cohorts (GAMBL reanalysis)

DLBCL

Entity Collection N mutated Incidence 95% CI
DLBCL GAMBL without Reddy 1,089 135 0.1240 [0.1044,0.1435]
DLBCL GAMBL with Reddy 2,088 213 0.1020 [0.089,0.115]
DLBCL BC 231 22 0.0952 [0.0574,0.1331]
DLBCL Dana-Farber 303 32 0.1056 [0.071,0.1402]
DLBCL NCI 470 72 0.1532 [0.1206,0.1858]
DLBCL Reddy 999 78 0.0781 [0.0614,0.0947]
DLBCL DLBCL_ICGC 85 9 0.1059 [0.0405,0.1713]

MCL

pathology Collection N mutated Incidence CI
MCL GAMBL 160 10 0.0616 [0.0244,0.0989]
MCL BC_MCL 103 7 0.0680 [0.0194,0.1166]
MCL Barcelona 57 3 0.0526 [0,0.1106]

FL

pathology Collection N mutated Incidence CI
FL GAMBL without Crouch 642 75 0.1168 [0.092,0.1417]
FL GAMBL with Crouch 1,189 137 0.1152 [0.0971,0.1334]
FL BC 379 54 0.1425 [0.1073,0.1777]
FL Kalmbach 164 14 0.0854 [0.0426,0.1281]
FL Crouch 547 62 0.1133 [0.0868,0.1399]
FL FL_ICGC 99 7 0.0707 [0.0202,0.1212]

Mutation pattern and selective pressure estimates

Entity Missense dN/dS Nonsense dN/dS Q value
BL 2.4685 0.0000 1
FL 11.0187 3.1989 0
DLBCL 7.5847 0.5576 0

CARD11 Hotspots

Chromosome Coordinate (hg19) ref>alt HGVSp
chr7 2979522 T>C E242G
chr7 2979521 T>A E242D
chr7 2979513 A>G L245P
chr7 2979508 T>C R247G
chr7 2979501 T>G Q249P
chr7 2979499 A>G S250P
chr7 2979495 A>G L251P
chr7 2979493 T>A K252*
chr7 2979486 T>C K254R
chr7 2979481 C>T D256N
chr7 2977614 T>C D357G
chr7 2977614 T>A D357V
chr7 2977604 C>A M360I
chr7 2977602 T>G Y361S
chr7 2977602 T>C Y361C

Visualizations

Protein

View coding variants in ProteinPaint hg19 or hg38

Genome

View all variants in GenomePaint hg19 or hg38

Expression

History

%%{init: { 'logLevel': 'debug', 'theme': 'dark' } }%% timeline title Publication timing 2008-03-03 : Lenz : DLBCL 2011-07-27 : Morin : DLBCL 2012-03-06 : Lohr : DLBCL 2012-04-01 : Yan : MZL 2013-01-01 : Zhang : DLBCL 2013-08-15 : Morin : DLBCL 2016-06-21 : Wu : MCL 2017-05-01 : Albuquerque : DLBCL 2017-10-10 : Reddy : DLBCL

References

1.
Lenz G, Davis RE, Ngo VN, Lam L, George TC, Wright GW, Dave SS, Zhao H, Xu W, Rosenwald A, Ott G, Müller-Hermelink HK, Gascoyne RD, Connors JM, Rimsza LM, Campo E, Jaffe ES, Delabie J, Smeland EB, Fisher RI, Chan WC, Staudt LM. Oncogenic CARD11 mutations in human diffuse large B cell lymphoma. Science. 2008 Mar;319(5870):1676–1679.
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
3.
Wu C, de Miranda NF, Chen L, Wasik AM, Mansouri L, Jurczak W, Galazka K, Dlugosz-Danecka M, Machaczka M, Zhang H, Peng R, Morin RD, Rosenquist R, Sander B, Pan-Hammarström Q. Genetic heterogeneity in primary and relapsed mantle cell lymphomas: Impact of recurrent CARD11 mutations. Oncotarget. 2016 Jun 21;7(25):38180–38190. PMCID: PMC5122381
4.
Yan Q, Huang Y, Watkins AJ, Kocialkowski S, Zeng N, Hamoudi RA, Isaacson PG, de Leval L, Wotherspoon A, Du MQ. BCR and TLR signaling pathways are recurrently targeted by genetic changes in splenic marginal zone lymphomas. Haematologica. 2012 Apr;97(4):595–598. PMCID: PMC3347666

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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