Table 2.

Genetic alterations of TGF-β pathway components in EBV-associated cancers identified by next-generation sequencing.

Cancer	Total Number of Cases	EBV Status	Genes	Alterations	Number of Cases with Alterations	References
NPC	56 primary tumours	Positive	SMAD3	Missense mutation	1 (primary tumour)	[118]
NPC	51 primary tumours 8 recurrent tumours 3 local metastatic tumours	Positive	TGF-β1	Missense mutation	1 (primary tumour)	[119]
			TGF-β2	Missense mutation	1 (primary tumour)
			TGFBR2	Missense mutation	1 (primary tumour)
NPC	78 primary tumours 11 local recurrent tumours 22 distant metastatic tumours	Positive	TGF-β1	Missense mutation	1 (primary tumour)	[120]
			TGF-β1	Nonsense mutation	1 (local recurrent tumour)
			TGF-β1	Silent mutation	1 (primary tumour)
			TGF-β2	Frame shift deletion	1 (local recurrent tumour)
			TGF-β2	Inversion	1 (primary tumour)
			TGFBR1	Missense mutation	1 (primary tumour) 1 (local recurrent tumour)
			TGFBR2	Inter chromosomal translocation	1 (primary tumour)
			SMAD3	Silent mutation	1 (local recurrent tumour)
			SMAD4	Missense mutation	1 (primary tumour)
			SMAD4	Nonsense mutation	1 (primary tumour)
			SMAD7	Missense mutation	1 (local recurrent tumour)
EBVaGC	134 primary tumours	Positive: n = 34 Negative: n = 100	TGFBR1	Nonsynonymous mutation	9 (EBV-positive) 8 (EBV-negative)	[121]
	AGS cell line	Before and after EBV infection		Missense mutation	EBV-infected AGS cells
EBVaGC	22 primary tumours	Positive	SMAD4	Missense mutation	2	[122]
HL	7 cell lines	Positive: L591 Negative: SUPHD1, L540, L428, L1236, KMH2, DEV	SMAD9	Missense mutation	1 (KMH2)	[123]
HL	5 cell lines	Negative (HDML2, KMH2, UH01, L540, L428)	TGF-β1	Amplification	2 (L540, L428)	[124]
			TGF-β2	Amplification	3 (KMH2, L540, L428)
				Deletion	1 (UH01)
			TGFBR2	Amplification	3 (KMH2, L540, L428)
			TGFBR3	Amplification	2 (KMH2, L428)
			SMAD1	Amplification	3 (KMH2, L540, L428)
				Deletion	2 (HDML2, UH01)
			SMAD5	Amplification	3 (KMH2, L540, L428)
DLBCL	73 primary tumours 21 DLBCL cell lines	Unreported	TGF-β1	Missense mutation	1 (primary tumours)	[125]
			TGF-β1	Intronic mutation	1 (primary tumours)
			TGFBR2	Intronic mutation	2 (primary tumours)
			TGFBR3	Intronic mutation	2 (primary tumours)
			SMAD9	Intronic mutation	1 (primary tumours)
DLBCL	51 primary tumours & immunochemotherapy-treated tumours	Unreported	TGF-β1	CNA	3 (treated tumours)	[126]
DLBCL	6 refractory & 7 responsive tumours to R-Chop	Negative	TGFBR2	Missense mutation	1 (refractory tumour)	[127]
DLBCL	47 relapsed/refractory tumours 65 primary tumours	Unreported	TGFBR2	Missense mutation	6 (relapsed/refractory tumours)	[128]
DLBCL	295 activated B-cell like DLBCL (ABC) 164 germinal-center B-cell like DLBCL (GCB) 115 unclassified DLBCL	Unreported	TGF-β1	Missense mutation	5 (4 ABC, 1 GCB)	[129]
				Truncated mutation	2 (ABC)
			TGF-β2	Truncated mutation	2 (1 ABC, 1 GCB)
			TGF-β3	Missense mutation	1 (ABC)
			TGFBR1	Missense mutation	1 (GCB)
			TGFBR2	Missense mutation	2 (1 ABC, 1 GCB)
				Truncated mutation	2 (1 GCB, 1 unclassified)
			TGFBR3	Missense mutation	2 (1 ABC, 1 unclassified)
				Truncated mutation	1 (GCB)
			SMAD1	Missense mutation	1 (ABC)
				Truncated mutation	1 (GCB)
			SMAD2	Missense mutation	3 (1 ABC, 1 GCB, 1 unclassified)
			SMAD4	Missense mutation	3 (2 ABC, 1 unclassified)
				Truncated mutation	1 (ABC)
			SMAD5	Missense mutation	5 (4 ABC, 1 GCB)
			SMAD6	Missense mutation	1 (GCB)
			SMAD7	Missense mutation	2 (1 ABC, 1 GCB)
			SMAD9	Truncated mutation	1 (ABC)