BTG2

Overview

BTG2 is one of a number of genes affected by aberrant somatic hypermutation in B-cell lymphomas, which complicates the interpretation of mutations at this locus. Mutations in the BTG2 gene have been implicated in the pathogenesis of diffuse large B-cell lymphoma (DLBCL), contributing to the development and progression of the disease. These mutations are a feature of the MCD genetic subgroup of DLBCL.¹ The biological function of BTG2 mutations and their role in lymphomagenesis remains poorly understood. A potential prognostic association with BTG2 mutations in primary testicular DLBCL has been reported but this has not yet been reproduced.²

Relevance tier by entity

Entity	Tier	Description
	2-a	aSHM target; Although recurrent, the relevance of mutations in BL is tenuous
	1-a	aSHM target and high-confidence DLBCL gene
	1-a	aSHM target and high-confidence FL gene

Mutation incidence in large patient cohorts (GAMBL reanalysis)

Entity	source	frequency (%)
BL	GAMBL genomes+capture	4.85
BL	Thomas cohort	4.20
BL	Panea cohort	9.90
DLBCL	GAMBL genomes	13.38
DLBCL	Schmitz cohort	17.23
DLBCL	Reddy cohort	9.21
DLBCL	Chapuy cohort	5.98
FL	GAMBL genomes	4.39

Mutation pattern and selective pressure estimates

Entity	aSHM	Significant selection	dN/dS (missense)	dN/dS (nonsense)
BL	Yes	No	6.152	42.280
DLBCL	Yes	Yes	3.562	10.265
FL	Yes	No	6.073	0.000

aSHM regions

chr_name	hg19_start	hg19_end	region	regulatory_comment
chr1	203274698	203275778	intron	active_promoter

[!NOTE] First described in BL in 2019 by Panea RI. First described in DLBCL in 2011 by Morin RD. First described in FL in 2011 by Morin RD

View coding variants in ProteinPaint hg19 or hg38

View all variants in GenomePaint hg19 or hg38

BTG2 Expression

References

1. Wright GW, Huang DW, Phelan JD, Coulibaly ZA, Roulland S, Young RM, Wang JQ, Schmitz R, Morin RD, Tang J, Jiang A, Bagaev A, Plotnikova O, Kotlov N, Johnson CA, Wilson WH, Scott DW, Staudt LM. A Probabilistic Classification Tool for Genetic Subtypes of Diffuse Large B Cell Lymphoma with Therapeutic Implications. Cancer Cell. 2020 Apr 13;37(4):551-568.e14. doi: 10.1016/j.ccell.2020.03.015. PMID: 32289277; PMCID: PMC8459709.
2. Guo D, Hong L, Ji H, Jiang Y, Lu L, Wang X, Huang H. The Mutation of BTG2 Gene Predicts a Poor Outcome in Primary Testicular Diffuse Large B-Cell Lymphoma. J Inflamm Res. 2022 Mar 10;15:1757-1769. doi: 10.2147/JIR.S341355. PMID: 35300216; PMCID: PMC8923029.
3. 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 SJ, 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. doi: 10.1038/nature10351. PMID: 21796119; PMCID: PMC3210554.