BCL7A

Overview

BCL7A protein interacts with components of the SWI/SNF chromatin remodeling complex, implicating it in chromatin remodeling processes essential for normal cellular function.¹ Mutations in the BCL7A gene have been identified in diffuse large B-cell lymphoma (DLBCL) and other B-cell lymphomas, implicating this gene in the pathogenesis of these cancers. Importantly, BCL7A 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. Due to the presence of some loss-of-function mutations, BCL7A has been described as a tumour-suppressor gene in DLBCL.³ The rate of DLBCLs with biallelic loss of this locus remains unclear.

Relevance tier by entity

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

Mutation incidence in large patient cohorts (GAMBL reanalysis)

Entity	source	frequency (%)
BL	GAMBL genomes+capture	5.31
BL	Thomas cohort	5.50
BL	Panea cohort	5.00
DLBCL	GAMBL genomes	7.65
DLBCL	Schmitz cohort	10.64
DLBCL	Reddy cohort	8.41
DLBCL	Chapuy cohort	6.41
FL	GAMBL genomes	13.86

Mutation pattern and selective pressure estimates

Entity	aSHM	Significant selection	dN/dS (missense)	dN/dS (nonsense)
BL	Yes	Yes	9.127	46.248
DLBCL	Yes	Yes	22.635	0.000
FL	Yes	Yes	55.348	146.110

aSHM regions

chr_name	hg19_start	hg19_end	region	regulatory_comment
chr12	122456912	122464036	TSS	poised_promoter

[!NOTE] First described in BL in 2019 by Grande BM

View coding variants in ProteinPaint hg19 or hg38

View all variants in GenomePaint hg19 or hg38

References

1. Ramos-Medina R, Montes-Moreno S, Maestre L, Cañamero M, Rodríguez-Pinilla M, Martínez-Torrecuadrada J, Piris MÁ, Majid A, Dyer MJ, Pulford K, Roncador G. BCL7A protein expression in normal and malignant lymphoid tissues. Br J Haematol. 2013 Jan;160(1):106-9. doi: 10.1111/bjh.12080. Epub 2012 Oct 9. PMID: 23043359.
2. 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. doi: 10.1182/blood-2018-09-871418. Epub 2019 Jan 7. PMID: 30617194; PMCID: PMC6428665.
3. Baliñas-Gavira C, Rodríguez MI, Andrades A, Cuadros M, Álvarez-Pérez JC, Álvarez-Prado ÁF, de Yébenes VG, Sánchez-Hernández S, Fernández-Vigo E, Muñoz J, Martín F, Ramiro AR, Martínez-Climent JA, Medina PP. Frequent mutations in the amino-terminal domain of BCL7A impair its tumor suppressor role in DLBCL. Leukemia. 2020 Oct;34(10):2722-2735. doi: 10.1038/s41375-020-0919-5. Epub 2020 Jun 24. PMID: 32576963.