TP53

Table of Contents

Experimental Evidence
Relevance tier by entity
Mutation incidence in large patient cohorts (GAMBL reanalysis)
- DLBCL
- FL
- BL
- MCL
Mutation pattern and selective pressure estimates
Expression
History
References

Experimental Evidence

Driver mutations affecting this gene in BL/FL/DLBCL have been experimentally demonstrated to cause a reduction or loss of function (LOF).¹

Relevance tier by entity

Entity	Tier	Description
	1	High-confidence BL gene
	1	High-confidence DLBCL gene
	1	High-confidence FL gene
	1	High-confidence MCL gene
	1	High-confidence MZL gene
	1	High-confidence PMBL gene

Mutation incidence in large patient cohorts (GAMBL reanalysis)

DLBCL

Entity	Collection	N	mutated	Incidence	95% CI
DLBCL	GAMBL without Reddy	1,089	242	0.2222	[0.1975,0.2469]
DLBCL	GAMBL with Reddy	2,088	351	0.1681	[0.1521,0.1841]
DLBCL	BC	231	56	0.2424	[0.1872,0.2977]
DLBCL	Dana-Farber	303	67	0.2211	[0.1744,0.2679]
DLBCL	NCI	470	105	0.2234	[0.1857,0.2611]
DLBCL	Reddy	999	109	0.1091	[0.0898,0.1284]
DLBCL	DLBCL_ICGC	85	14	0.1647	[0.0859,0.2436]

FL

pathology	Collection	N	mutated	Incidence	CI
FL	GAMBL without Crouch	642	38	0.0592	[0.0409,0.0774]
FL	GAMBL with Crouch	1,189	75	0.0631	[0.0493,0.0769]
FL	BC	379	22	0.0580	[0.0345,0.0816]
FL	Kalmbach	164	9	0.0549	[0.02,0.0897]
FL	Crouch	547	37	0.0676	[0.0466,0.0887]
FL	FL_ICGC	99	7	0.0707	[0.0202,0.1212]

BL

pathology	Collection	N	mutated	Incidence	CI
BL	GAMBL without Panea	309	133	0.4286	[0.3742,0.4829]
BL	GAMBL without ICGC/Zhou	320	126	0.3931	[0.3397,0.4465]
BL	GAMBL with Panea	410	177	0.4303	[0.3829,0.4776]
BL	BLGSP	219	82	0.3744	[0.3103,0.4385]
BL	Zhou/ICGC	90	51	0.5667	[0.4643,0.669]
BL	Panea	101	44	0.4356	[0.3389,0.5323]

MCL

pathology	Collection	N	mutated	Incidence	CI
MCL	GAMBL	160	16	0.0992	[0.0529,0.1455]
MCL	BC_MCL	103	11	0.1068	[0.0471,0.1664]
MCL	Barcelona	57	5	0.0877	[0.0143,0.1612]

Mutation pattern and selective pressure estimates

Entity	Missense dN/dS	Nonsense dN/dS
BL	109.5835	55.7294
FL	39.4035	45.2274
DLBCL	21.2397	39.7863

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Expression

History

%%{init: { 'logLevel': 'debug', 'theme': 'dark' } }%% timeline title Publication timing 2004-03-01 : Wilda : BL 2011-07-27 : Morin : FL 2012-08-27 : Rossi : MZL 2013-11-05 : Be : MCL 2018-05-31 : Tiacci : PMBL

References

Kato S, Han SY, Liu W, Otsuka K, Shibata H, Kanamaru R, Ishioka C. Understanding the function-structure and function-mutation relationships of P53 tumor suppressor protein by high-resolution missense mutation analysis. Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8424–8429. PMCID: PMC166245

Beà S, Valdés-Mas R, Navarro A, Salaverria I, Martín-Garcia D, Jares P, Giné E, Pinyol M, Royo C, Nadeu F, Conde L, Juan M, Clot G, Vizán P, Croce LD, Puente DA, López-Guerra M, Moros A, Roue G, Aymerich M, Villamor N, Colomo L, Martínez A, Valera A, Martín-Subero JI, Amador V, Hernández L, Rozman M, Enjuanes A, Forcada P, Muntañola A, Hartmann EM, Calasanz MJ, Rosenwald A, Ott G, Hernández-Rivas JM, Klapper W, Siebert R, Wiestner A, Wilson WH, Colomer D, López-Guillermo A, López-Otín C, Puente XS, Campo E. Landscape of somatic mutations and clonal evolution in mantle cell lymphoma. PNAS. 2013;110(45):18250–18255.

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

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

Rossi D, Trifonov V, Fangazio M, Bruscaggin A, Rasi S, Spina V, Monti S, Vaisitti T, Arruga F, Famà R, Ciardullo C, Greco M, Cresta S, Piranda D, Holmes A, Fabbri G, Messina M, Rinaldi A, Wang J, Agostinelli C, Piccaluga PP, Lucioni M, Tabbò F, Serra R, Franceschetti S, Deambrogi C, Daniele G, Gattei V, Marasca R, Facchetti F, Arcaini L, Inghirami G, Bertoni F, Pileri SA, Deaglio S, Foà R, Dalla-Favera R, Pasqualucci L, Rabadan R, Gaidano G. The coding genome of splenic marginal zone lymphoma: Activation of NOTCH2 and other pathways regulating marginal zone development. J Exp Med. 2012 Aug 27;209(9):1537–1551. PMCID: PMC3428941

Tiacci E, Ladewig E, Schiavoni G, Penson A, Fortini E, Pettirossi V, Wang Y, Rosseto A, Venanzi A, Vlasevska S, Pacini R, Piattoni S, Tabarrini A, Pucciarini A, Bigerna B, Santi A, Gianni AM, Viviani S, Cabras A, Ascani S, Crescenzi B, Mecucci C, Pasqualucci L, Rabadan R, Falini B. Pervasive mutations of JAK-STAT pathway genes in classical Hodgkin lymphoma. Blood. 2018 May 31;131(22):2454–2465. PMCID: PMC6634958

Wilda M, Bruch J, Harder L, Rawer D, Reiter A, Borkhardt A, Woessmann W. Inactivation of the ARF-MDM-2-p53 pathway in sporadic Burkitt’s lymphoma in children. Leukemia. 2004 Mar;18(3):584–588.