Table 5.

Association of APOBEC3 expression and APOBEC3-induced mutations with clinical outcomes by cancer type

Cancer type	APOBEC3(s)*	Outcome type	Immunotherapy context?	Clinical outcome	References
Adrenal	3B	Adverse	No	Shorter overall and disease-free survival	[44]
Bladder	3B	Positive	No	Longer survival with APOBEC3B-enhancing SNP (rs101497)	[61]
	Mutation burden	Positive	No	Longer survival in muscle-invasive disease cohort	[170]
	Mutation burden	Positive	No	Longer survival	[46]
	3D and 3H	Positive	No	Better overall survival	[171]
	3B	Adverse	No	Shorter progression-free survival with mutagenic A3B1 isoform	[1]
	Mutation burden	Adverse	No	Higher risk of class 2a tumors and poor outcomes for non-muscle invasive disease	[172]
	3A and 3B	Adverse	No	Increased risk of class 2a tumors	[173]
	Mutation burden	Positive	Yes	Longer survival overall and better response to immune checkpoint blockade therapy	[160]
	Mutation burden	Positive	Yes	Increased responsiveness to immunotherapy	[174]
Breast	3A	Adverse	No	Advanced tumor stage, higher histological grade, and more lymph node involvement	[64]
	3A	Adverse	No	Shorter overall survival	[175]
	3B	Adverse	No	Higher tumor grade with lymph node involvement and worse prognosis	[105]
	3B	Adverse	No	Higher nuclear grade and more frequent lymph node metastasis	[176]
	3B	Adverse	No	Shorter disease-free, metastasis-free, and overall survival. Lower overall survival in ER+ subgroup	[177]
	3B	Adverse	No	Shorter survival in ER+ but not ER- group	[161]
	3B	Adverse	No	Lower recurrence-free survival in a combined analysis and ER+ subgroup	[178]
	3A/B	Adverse	No	Higher histological grade with 3A/B chimera	[64]
	3A-H	Mixed	No	Aggressive pathology and shorter survival (3A and 3B). Improved survival (3C-H)	[48]
	3B	Mixed	No	Shorter replace-free, metastasis-free, and overall survival (mRNA). Increased disease-free survival (protein)	[165]
	3B	Mixed	No	Higher nuclear grade and Ki-67 labeling index, but improved responsiveness to neoadjuvant chemotherapy	[179]
	Mutation burden	Adverse (overall)	Yes	Shorter survival with first-line endocrine and CDK4/6i therapy, but improved response to immune checkpoint blockade therapy	[180]
		Positive (immunotherapy)
	Mutation burden	Positive	Yes	Improved response to immunotherapy	[181]
Esophageal	3B	Adverse/none	No	Higher histological grade	[39]
Gastric	3B	Adverse (overall)	No	Shorter overall and progression-free survival, but improved response to fluorouracil-based adjuvant chemotherapy and PD-1 blockade therapy	[37]
		Positive (immunotherapy)	Yes
	3B	Adverse	No	Aggressive pathology and poor survival	[38]
Glioma	3B, 3C, 3D, 3F, 3G, 3H	Adverse	No	Poor prognosis, especially in the low-grade subtype	[51]
Head and neck	Mutation burden	Positive	Yes	Improved responsiveness to immunotherapy	[174]
Lung	3B	Adverse	No	Shorter survival	[182]
	3B	Adverse	No	Shorter disease-free and overall survival with more with lymph node involvement and higher TNM stage	[183]
	3B	Adverse	No	Shorter overall survival	[175]
	Mutation burden	Adverse	No	Worse overall survival	[184]
	Mutation burden	Adverse	No	Signature 2 (but not 13) burden associated with poor prognosis	[185]
	3B	None	No	No association with pathological features or clinical outcomes	[54]
	Mutation burden	Positive	Yes	Increased response to immune checkpoint blockade therapy	[166]
	3B	Positive	Yes	Improved responsiveness to immune checkpoint blockade therapy	[36]
Nasopharyngeal	3B	Adverse	No	Aggressive disease and poor outcomes	[55]
Neuroendocrine tumor	3B	Adverse	No	More lymph node metastasis	[40]
Ovarian	Mutation burden	Positive	No	Improved progression-free and overall survival	[186]
	3B	Adverse	No	Shorter disease-free and overall survival	[42]
	3B	Positive	No	Longer progression-free (significant) and overall (not significant)	[41]
	3G	Positive	No	Favorable clinical outcomes with A3G, but no association for A3B	[167]
Pancreatic	3G	None	No	No association with tumor stage, tumor type, or prognosis	[49]
Renal	3B	Adverse	No	More frequent recurrence	[169]

^*Where applicable, “mutation burden” refers to APOBEC3-induced mutation burden