Table of Contents

Overview

Although CDKN2A aberrations are common in DLBCL, this gene is predominantly affected by copy number alterations. One study found that deletions of the CDKN2A locus occur in about one-third of DLBCL patients.1 The mutation pattern in DLBCL and FL implies the preferential accumulation of inactivating mutations. This gene has some recurrent sites of mutations (hotspots) with the most common mutation causing a truncation at codon 80 (R80*).

Experimental Evidence

Driver mutations affecting this gene in DLBCL have been experimentally demonstrated to cause a reduction or loss of function (LOF).2

Relevance tier by entity

Entity Tier Description
BL 2 Role of CDKN2A mutations in BL requires confirmation
DLBCL 1 High-confidence DLBCL gene
MZL 2 Role of CDKN2A mutations in MZL requires confirmation
PMBL 2 Role of CDKN2A mutations in PMBL requires confirmation

Mutation incidence in large patient cohorts (GAMBL reanalysis)

DLBCL

Entity Collection N mutated Incidence 95% CI
DLBCL GAMBL without Reddy 1,089 36 0.0331 [0.0224,0.0437]
DLBCL GAMBL with Reddy 2,088 46 0.0220 [0.0157,0.0283]
DLBCL BC 231 5 0.0216 [0.0029,0.0404]
DLBCL Dana-Farber 303 4 0.0132 [3e-04,0.0261]
DLBCL NCI 470 23 0.0489 [0.0294,0.0684]
DLBCL Reddy 999 10 0.0100 [0.0038,0.0162]
DLBCL DLBCL_ICGC 85 4 0.0471 [0.002,0.0921]

BL

pathology Collection N mutated Incidence CI
BL GAMBL without Panea 309 3 0.0096 [0,0.0205]
BL GAMBL without ICGC/Zhou 320 5 0.0117 [0,0.0235]
BL GAMBL with Panea 410 6 0.0116 [0.0012,0.0219]
BL BLGSP 219 2 0.0091 [0,0.0217]
BL Zhou/ICGC 90 1 0.0111 [0,0.0328]
BL Panea 101 3 0.0297 [0,0.0628]

FL

pathology Collection N mutated Incidence CI
FL GAMBL without Crouch 642 8 0.0125 [0.0039,0.021]
FL GAMBL with Crouch 1,189 14 0.0118 [0.0056,0.0179]
FL BC 379 6 0.0158 [0.0033,0.0284]
FL Kalmbach 164 2 0.0122 [0,0.029]
FL Crouch 547 6 0.0110 [0.0022,0.0197]
FL FL_ICGC 99 0 0.0010 [0,0.0073]

Mutation pattern and selective pressure estimates

Entity Isoform aSHM Significant selection dN/dS (missense) dN/dS (nonsense)
BL CDKN2A.p14arf No No 10.947 72.708
DLBCL CDKN2A.p14arf No Yes 19.055 102.121
FL CDKN2A.p14arf No No 0.000 117.964
BL CDKN2A.p16INK4a No No 2.931 104.823
DLBCL CDKN2A.p16INK4a No Yes 5.631 442.466
FL CDKN2A.p16INK4a No No 0.000 159.196

CDKN2A Hotspots

Chromosome Coordinate (hg19) ref>alt HGVSp
chr9 21971120 G>A R80*

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 2013-08-15 : Morin : DLBCL 2016-09-08 : Spina : MZL 2017-10-10 : Reddy : DLBCL 2018-04-12 : Schmitz : DLBCL 2019-03-21 : Grande : BL 2021-05-05 : Hubschmann : DLBCL

References

1.
Spina V, Khiabanian H, Messina M, Monti S, Cascione L, Bruscaggin A, Spaccarotella E, Holmes AB, Arcaini L, Lucioni M, Tabbò F, Zairis S, Diop F, Cerri M, Chiaretti S, Marasca R, Ponzoni M, Deaglio S, Ramponi A, Tiacci E, Pasqualucci L, Paulli M, Falini B, Inghirami G, Bertoni F, Foà R, Rabadan R, Gaidano G, Rossi D. The genetics of nodal marginal zone lymphoma. Blood. 2016 Sep 8;128(10):1362–1373. PMCID: PMC5016706
2.
Kannengiesser C, Brookes S, del Arroyo AG, Pham D, Bombled J, Barrois M, Mauffret O, Avril MFM, Chompret A, Lenoir GM, Sarasin A, French Hereditary Melanoma Study Group, Peters G, Bressac-de Paillerets B. Functional, structural, and genetic evaluation of 20 CDKN2A germ line mutations identified in melanoma-prone families or patients. Hum Mutat. 2009 Apr;30(4):564–574.
3.
Grande BM, Gerhard DS, Jiang A, Griner NB, Abramson JS, Alexander TB, Allen H, Ayers LW, Bethony JM, Bhatia K, Bowen J, Casper C, Choi JK, Culibrk L, Davidsen TM, Dyer MA, Gastier-Foster JM, Gesuwan P, Greiner TC, Gross TG, Hanf B, Harris NL, He Y, Irvin JD, Jaffe ES, Jones SJM, Kerchan P, Knoetze N, Leal FE, Lichtenberg TM, Ma Y, Martin JP, Martin MR, Mbulaiteye SM, Mullighan CG, Mungall AJ, Namirembe C, Novik K, Noy A, Ogwang MD, Omoding A, Orem J, Reynolds SJ, Rushton CK, Sandlund JT, Schmitz R, Taylor C, Wilson WH, Wright GW, Zhao EY, Marra MA, Morin RD, Staudt LM. Genome-wide discovery of somatic coding and noncoding mutations in pediatric endemic and sporadic Burkitt lymphoma. Blood. 2019;133(12):1313–1324. PMCID: PMC6428665
4.
Morin RD, Mungall K, Pleasance E, Mungall AJ, Goya R, Huff RD, Scott DW, Ding J, Roth A, Chiu R, Corbett RD, Chan FC, Mendez-Lago M, Trinh DL, Bolger-Munro M, Taylor G, Hadj Khodabakhshi A, Ben-Neriah S, Pon J, Meissner B, Woolcock B, Farnoud N, Rogic S, Lim EL, Johnson NA, Shah S, Jones S, Steidl C, Holt R, Birol I, Moore R, Connors JM, Gascoyne RD, Marra MA. Mutational and structural analysis of diffuse large B-cell lymphoma using whole-genome sequencing. Blood. 2013 Aug 15;122(7):1256–1265. PMCID: PMC3744992

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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