Table 1.

Altered DNA Repair Pathway genes and their effect on MM.

DNA Repair Pathway	Altered Gene in MM	Type of Alteration	Resulting Effect	Reference
Base Excision Repair	OGG1	SNP	Low BER activity = increased risk of MM progression	[19]
	MUTYH	SNP	Shorter survival	[19]
	APE1	SNP	Shorter survival	[19]
	TDG	Hypermethylation resulting in lower gene expression	less efficient DNA repair in response to OH induced DNA damage	[20]
Nucleotide Excision Repair	hHR23B/RAD23B	Epigenetic silencing in KAS-6/1	Genetic instability during early B cell maturation	[21]
	ERCC3 and XPC	Knockdown	Impairs NER and increases sensitivity to melphalan	[22]
	ERR5 and XPA	SNP	Longer survival following treatment with autologous stem cell transplantation	[23]
	XRCC1	SNP rs25489 (Arg → His)	Diminished repair capacity relevant to MM etiology	[24]
	ERCC2 N312D and ERCC2 K751Q	Polymorphism resulting in an amino acid substitution	Increased DNA adducts, low repair capacity associated with sensitivity to high dose alkylating chemotherapy	[25]
Mismatch Repair	hMLH1	Hypermethylation associated with decreased protein expression but not loss of MMR capacity	Plays a role in the transition of MGUS to MM and poorer survival	[26,27]
	MSI	Deficiencies in MMR repair proteins	Possible contributory role in MM disease progression	[28]
Homologous Recombination	ATM and BRCA2	Deleterious mutations	Negative impact on survival	[29]
	ATM	Mutations	Impaired progression-free survival, Impaired overall survival	[30]
	RAD51	High expression	Chemoresistance and poor patient survival	[31]
	RAD51	DNA Repair Score	Poor event free and overall survival	[32]
	PARP1	Higher mRNA expression	Poor survival in MM	[33]
Non-Homologous End Joining	LIG4	SNP A3V and T9I resulting in amino acid substitution	Two-fold reduction in risk of developing MM	[34]
	XRCC4	SNP affecting mRNA transcript or altering expression	Alters the risk of developing myeloma	[35]
	XRCC5	SNP causing errors in alternative splicing, affect mRNA stability and translation
Fanconi Anaemia	FANCF and RAD51C	Increase in expression of genes	Acquired Melphalan resistance in 8226/LR5	[36]
	NEIL1	Downregulation	Increased efficiency of DSB and ss break repair associated with Melphalan resistance	[37]
	FANCI, FANCA, FANCD2, and BRCA	Alterations such as Missense Mutations	Related to MM patients in relapse	[38]
	FANCI, FANB, RAD51, and BRCA1	Increased expression	Characteristics of residual myeloma plasma cells (cells responsible for relapse, drug resistance, and having stem cell-like characteristics including altered cell metabolism, increased drug efflux, ALDH1 activity, and propagation)	[39]
Overlapping pathways	MMSET	Overexpression	Poorer prognosis and response to therapy compared to other MM subtypes	[40]
	AID	Absent in MM and SMM patient samples	Early and common driver mutational process	[41]