Role of RNA Splicing Mutations in Diffuse Large B Cell Lymphoma

Figures & data

Figure 1 A schematic representative pre-mRNA, coding and non-coding sequence and splicing site.

Figure 2 Splicing regulation mechanism.

Figure 3 Schematic representation of constitutive and alternative splicing dysregulation.

Figure 4 Schematic representation of pathological mechanisms DLBCL in splicing mutation.

Table 1 Summarizes the Role of Splicing Mutation in Different Genes in DLBCL as Well as Their Mechanisms

Splicing Mutation	List of Gene Affected	Possible Mechanism Involved for DLBCL Pathogenesis	References
Exon skipping	MYD88, NOTCH1, SGK1, ZEB2, NOTCH1, CD70, FOXP1, CYLD, EBF1 and PIM1	Inhibition of tumor suppressor role	[4,6,7,27,30,36,51]
	MYD88, POU2AF1, EBF1, TNFAIP3, PTPN1, NFKBIE, NOTCH1 and SGK1	Inhibition of B cell differentiation	[23,30,34]
	EBF1 and PIM1	Activation of oncogene	[56,58]
	CD58, PIM1, CD37, CD70, B2M and PTPN1	Altered cell apoptosis	[4,7,25,30,51]
	GRHPR and STXBP2	Detail mechanism requires further study	[6,72]
Mutant splicing site	BCL7A, SGK1, ZEB2, CARD1, SGK1¸ B2M, CYLD PRDM1 and ATM	Inhibition of tumor suppressor role	[4,7,25,30,34,51]
	CARD1, SGK1, TNFAIP3, ZEB2 and PRDM1	Inhibition of B cell differentiation	[4,27,31,35,49–51]
	TP53, ETV6, CD83, TNFRSF14, ZEB2, CD37 and CD58	Altered cell apoptosis	[7,8,27,39]
	BCL7A and TP53	Altered DNA repair	[54,55]
	BCL7A	Activation of oncogene	[7,8,27]
	TBLIX2D, MYO1E, NYKBIA and TMSB4X	Detail mechanism requires further study	[7,27,30,45,73]
	PRDM1	Over proliferation of B cell	[7,51]
Intron retention	CARD1, CD79B, NOTCH1, FOXP1, SGK1, ZEB2 and PIM1	Inhibition of tumor suppressor role	[7,27]
	CARD1, CD79B, NOTCH1, FOXP1, SGK1, ZEB2 and DUSP2	Inhibition of B cell differentiation	[7,52]
	MYO1E, PABPC1, ZFP36L1 and KMT2D	Detail mechanism requires further study	[6]
Cryptic splice site	PIM1, CYLD and SGK1	Inhibition of tumor suppressor role	[4,7,30]
	GRHPR, LAPTM5 and TMSB4X	Detail mechanism requires further study	[7,30]
Alternative isoform	MYD88, SGK1, EBF1 and TNFAIP3	Inhibition of tumor suppressor role	[4,27,31,35,49–51]
	MYD88 and SGK1	Inhibition of B cell differentiation	[47,48]
	FAS and TP53	Altered cell apoptosis	[4,7]
	EBF1	Activation of oncogene	[6]
	TBL1XR1 and TCL1A	Detail mechanism requires further study	[4,30,52,74]
Splice factor mutation	SF1

Abbreviations: BCL7A, B-cell lymphoma 7 protein family member A; CD79B, cluster of differentiation 79B; MYD88, myeloid differentiation primary response gene 88; TP53, tumor protein P53; STAT, signal transducer and activator of transcription; SGK1, serum- and glucose-regulated kinase1; CARD11, caspase recruitment domain-containing protein 11; ZFP36L1, zinc finger proteins 36L1; PRDM1, PR domain zinc finger protein 1; POU2AF1, pou class 2 associating factor 1; NOTCH1, neurogenic locus notch homolog protein 1; FOXP1, Forkhead box protein P1; ETV6, ETS translocation variant 6; CD83, cluster of differentiation 83; TNFRSF14, tumor necrosis factor receptor superfamily member 14; CD, Cluster of Differentiation; MYO1E, Myosin-Ie; DUSP2, dual specificity protein phosphatase 2; LAPTM5, lysosomal-associated transmembrane protein 5; KMT2D, histone-lysine N-methyltransferase 2D; TCL1A, T-cell leukemia/lymphoma protein 1A; PIM1, proto-oncogene serine/threonine-protein kinase1.

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