APOBEC3-mediated mutagenesis in cancer: causes, clinical significance and therapeutic potential

Table 3 Recurrent APOBEC3-induced somatic mutations and copy number alterations in cancer

Mutation type	Gene name	Gene type	Amino acid alteration	Cancer type(s)	References
Coding	EGFR*	Oncogene	T790M	Lung	[82, 141]
	FGFR3	Oncogene	S249C	Bladder, cervical, HNSCC, and lung	[127, 129,130,131,132]
	MEK2	Oncogene	L46F	Melanoma	[82, 142]
	PIK3CA	Oncogene	E545K	Bladder, breast, cervical, colorectal, esophageal, HNSCC, and lung	[39, 132,133,134,135,136,137]
	PIK3CA	Oncogene	E542K	Bladder, breast, cervical, colorectal, esophageal, HNSCC, and lung	[39, 132, 133, 135, 137,138,139,140]
	FBXW7	Tumor suppressor	R505G	HNSCC, upper digestive tract, urinary tract, and lung	[132, 143]
Non-coding regulatory	ADGR6/GPR126	Oncogene	N/A	Bladder	[33, 144, 145]
	TBC1D12	Oncogene		Bladder and breast	[144, 147]
	LMO1	Oncogene		T-Cell acute lymphoblastic leukemia	[146]
	PLEKHS1	Oncogene		Bladder and breast	[144, 147]
	WDR74**	Oncogene		Bladder and breast	[144, 147]
	LEPROTL1	Unknown		Bladder and breast	[144, 155]
Copy number amplification	AGAP2	Oncogene	N/A	Glioma	[51]
	CDK4	Oncogene
	EGFR	Oncogene
	MAPKAPK2	Oncogene
	USP15	Oncogene
Not specified***	EGFR	Oncogene	N/A	Bladder, breast, HNSCC, and lung	[148]
	PTEN	Tumor suppressor
	TP53	Tumor suppressor

^*C-to-T mutation that is not in the preferred APOBEC3 motif but has been hypothesized to be a rare APOBEC3-induced mutation that is highly selected for given its strong oncogenic effects
^**Mutation has a less clear association with APOBEC3s and may arise from other mutational processes
^***Subclonal mutations in cancer driver genes, but the mutations are not specified as coding or non-coding

ISSN: 1756-8722