CDKN2A

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*).

History

Mutations in this gene were first described in DLBCL and FL in 2013 by Morin et al² and in BL in 2019 by Grande et al.³

%%{init: { 'logLevel': 'debug', 'theme': 'dark' } }%% timeline title Publication timing 2013-08-15 : Morin : DLBCL 2016-09-08 : Spina : MZL 2019-03-21 : Grande : BL

Relevance tier by entity

Entity	Tier	Description
	1	high-confidence PMBL/cHL/GZL gene
	2	relevance in MZL not firmly established
	1	high-confidence DLBCL gene
	2	relevance in BL not firmly established

Mutation incidence in large patient cohorts (GAMBL reanalysis)

Entity	source	frequency (%)
DLBCL	GAMBL genomes	3.25
DLBCL	Schmitz cohort	4.89
DLBCL	Reddy cohort	1.00
DLBCL	Chapuy cohort	1.71
BL	GAMBL genomes+capture	1.85
BL	Thomas cohort	3.00
BL	Panea cohort	3.00

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*

View coding variants in ProteinPaint hg19 or hg38

View all variants in GenomePaint hg19 or hg38

CDKN2A Expression

References

Guney S, Jardin F, Bertrand P, Mareschal S, Parmentier F, Picquenot JM, Tilly H, Bastard C. Several mechanisms lead to the inactivation of the CDKN2A (P16), P14ARF, or CDKN2B (P15) genes in the GCB and ABC molecular DLBCL subtypes. Genes Chromosomes Cancer. 2012 Sep;51(9):858-67. doi: 10.1002/gcc.21970. Epub 2012 May 23. PMID: 22619049.
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
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 Mar 21;133(12):1313–1324.