Table of Contents

Overview

The relevance of NOTCH1 mutations in various malignancies has been well established. However, due to minimal support in the original primary data and very few mutations reported in subsequent BL studies, this gene is very unlikely to be relevant in BL.

Experimental Evidence

Driver mutations affecting this gene in DLBCL have been experimentally demonstrated to cause a gain of function (GOF).1

Relevance tier by entity

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Warnings

The variants reported in this gene in BL failed QC

Mutation incidence in large patient cohorts (GAMBL reanalysis)

DLBCL

Entity Collection N mutated Incidence 95% CI
DLBCL GAMBL without Reddy 1,089 61 0.0560 [0.0424,0.0697]
DLBCL GAMBL with Reddy 2,088 95 0.0455 [0.0366,0.0544]
DLBCL BC 231 6 0.0260 [0.0055,0.0465]
DLBCL Dana-Farber 303 12 0.0396 [0.0176,0.0616]
DLBCL NCI 470 42 0.0894 [0.0636,0.1152]
DLBCL Reddy 999 34 0.0340 [0.0228,0.0453]
DLBCL DLBCL_ICGC 85 1 0.0118 [0,0.0347]

MCL

pathology Collection N mutated Incidence CI
MCL GAMBL 160 9 0.0561 [0.0205,0.0918]
MCL BC_MCL 103 6 0.0583 [0.013,0.1035]
MCL Barcelona 57 3 0.0526 [0,0.1106]

BL

pathology Collection N mutated Incidence CI
BL GAMBL without Panea 309 5 0.0154 [0.0017,0.0292]
BL GAMBL without ICGC/Zhou 320 15 0.0196 [0.0046,0.0346]
BL GAMBL with Panea 410 17 0.0201 [0.0067,0.0335]
BL BLGSP 219 3 0.0137 [0,0.0291]
BL Zhou/ICGC 90 2 0.0222 [0,0.0527]
BL Panea 101 12 0.1188 [0.0557,0.1819]

Mutation pattern and selective pressure estimates

Entity Missense dN/dS Nonsense dN/dS Q value
BL 0.9748 0.000 1.0000
FL 0.6272 0.000 1.0000
DLBCL 0.7026 1.642 0.0913

NOTCH1 Hotspots

Chromosome Coordinate (hg19) ref>alt HGVSp
chr9 139401207 C>T V1288I
chr9 139401199 G>C D1290E

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Expression

Representative Mutations

BL

Rating ★ ☆ ☆ ☆ ☆

All Mutations

BL

1061 1096 324 508 513

History

%%{init: { 'logLevel': 'debug', 'theme': 'dark' } }%% timeline title Publication timing 2011-07-31 : Pasqualucci : DLBCL 2012-08-27 : Rossi : MZL 2012-12-01 : Love : BL 2013-11-05 : Bea : MCL

References

1.
Ryan RJH, Petrovic J, Rausch DM, Zhou Y, Lareau CA, Kluk MJ, Christie AL, Lee WY, Tarjan DR, Guo B, Donohue LKH, Gillespie SM, Nardi V, Hochberg EP, Blacklow SC, Weinstock DM, Faryabi RB, Bernstein BE, Aster JC, Pear WS. A B Cell Regulome Links Notch to Downstream Oncogenic Pathways in Small B Cell Lymphomas. Cell Rep. 2017 Oct 17;21(3):784–797. PMCID: PMC5687286
2.
Love C, Sun Z, Jima D, Li G, Zhang J, Miles R, Richards KL, Dunphy CH, Choi WWL, Srivastava G, Lugar PL, Rizzieri DA, Lagoo AS, Bernal-Mizrachi L, Mann KP, Flowers CR, Naresh KN, Evens AM, Chadburn A, Gordon LI, Czader MB, Gill JI, Hsi ED, Greenough A, Moffitt AB, McKinney M, Banerjee A, Grubor V, Levy S, Dunson DB, Dave SS. The genetic landscape of mutations in Burkitt lymphoma. Nat Genet. 2012 Dec;44(12):1321–1325. PMCID: PMC3674561
3.
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

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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