GRB2

GRB2

Overview

GRB2 (Growth factor receptor-bound protein 2) is an adaptor protein that links receptor tyrosine kinases to the Ras signaling pathway through its SH2 and SH3 domains. The mutation pattern in DLBCL implies the preferential accumulation of inactivating mutations. While direct evidence of GRB2 mutations in DLBCL is limited, its established role in other cancers and signal transduction pathways suggests that it may contribute to lymphomagenesis. Further research is needed to elucidate its specific role in DLBCL.

History

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timeline
    title Publication timing
      2011-07-31 : Pasqualucci : DLBCL
      2019-09-26 : Panea : BL

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Relevance tier by entity

Entity	Tier	Description
	1	high-confidence DLBCL gene
	2	relevance in BL seems unlikely

Mutation incidence in large patient cohorts (GAMBL reanalysis)

Entity	source	frequency (%)
DLBCL	GAMBL genomes	3.25
DLBCL	Schmitz cohort	2.77
DLBCL	Reddy cohort	1.50
DLBCL	Chapuy cohort	2.99
BL	GAMBL genomes+capture	0.46
BL	Thomas cohort	0.40
BL	Panea cohort	1.00

Mutation pattern and selective pressure estimates

Entity	aSHM	Significant selection	dN/dS (missense)	dN/dS (nonsense)
DLBCL	No	Yes	33.029	168.982
FL	No	No	8.575	0.000
BL	No	No	7.253	0.000

View coding variants in ProteinPaint hg19 or hg38

View all variants in GenomePaint hg19 or hg38

GRB2 Expression

References

1. Pasqualucci L, Trifonov V, Fabbri G, Ma J, Rossi D, Chiarenza A, Wells VA, Grunn A, Messina M, Elliot O, Chan J, Bhagat G, Chadburn A, Gaidano G, Mullighan CG, Rabadan R, Dalla-Favera R. Analysis of the coding genome of diffuse large B-cell lymphoma. Nat Genet. 2011 Jul 31;43(9):830–837. PMCID: PMC3297422
2. Panea R, Love C, Shingleton JR, Reddy A, Bailey J, Moormann A, Otieno J, Ong’echa J, Oduor C, Schroêder K, Masalu N, Chao N, Agajanian M, Major M, Fedoriw Y, Richards K, Rymkiewicz G, Miles R, Alobeid B, Bhagat G, Flowers C, Ondrejka S, Hsi E, Choi W, Au-Yeung R, Hartmann W, Lenz G, Meyerson H, Lin YY, Zhuang Y, Luftig M, Waldrop A, Dave T, Thakkar D, Sahay H, Li G, Palus B, Seshadri V, Kim S, Gascoyne R, Levy S, Mukhopadhyay M, Dunson D, Dave S. The whole genome landscape of Burkitt lymphoma subtypes. Blood. 2019;