Table 1.

Type and frequency of DNA repair alterations in solid tumors

Alterations
Cancer typeGeneTypeFrequencyReferences
Non–small cell lung cancerBRCA1Reduced mRNA and protein expression44%(68)
FANCFPromoter methylation14%(69)
ATMSomatic mutations6%(69)
MSH2Reduced protein expression18%–38%(69)
ERCC1Reduced protein expression22%–66%(69)
RRM1Loss of heterozygosity65%(69)
Small-cell lung cancerPOLD4*Reduced mRNA expressionN.R.(70)
Clear-cell renal cell carcinomaATMSomatic mutations3%(71)
NSB1Somatic mutations0.5%
MLH1Homozygous deletion3%–5%(72)
MSH2Promoter hypermethylationN.R.(73)
Urothelial carcinomaBRCA1Somatic mutations14%(74–76)
BRCA2Somatic mutations14%
PALB2Somatic mutations14%
ATMSomatic mutations29%
MSH2Loss of protein expression3%(77)
ERCC2Somatic mutations12%(78)
Head and neck cancerFANCB*Promoter methylation31%(79)
FANCF*Promoter methylation15%
FANCJReduced protein expression (IHC)N.R.
FANCMReduced protein expression (IHC)N.R.
BRCA1Reduced protein expression (IHC)N.R.
BRCA2Reduced protein expression (IHC)N.R.
FANCD2Reduced protein expression (IHC)N.R.
Ovarian cancerBRCA1/BRCA2Germline mutations15%(80, 81)
Somatic mutations35%
Promoter methylation11%–35%
FANCFPromoter methylationN.R.
FANCD2Reduced protein expressionN.R.
BARD1Germline mutations6%(82)
BRIP1Germline mutations6%
PALB2Germline mutations6%
MRE11Germline mutations6%
RAD50Germline mutations6%
RAD51CGermline mutations6%
NSB1Germline mutations6%
MSH6Inactivating mutations6%(82)
Triple-negative breast cancerBRCA1Germline mutations5%–10%(80, 83)
BRCA2Somatic mutations10%
Gastric cancerMLH1Loss of protein expression (IHC)18%(84)
Promoter hypermethylation15%
MSH2Loss of protein expression (IHC)3%
MMR-deficient colorectal cancerMRE11Somatic mutations75%(34, 85, 86)
RAD50Somatic mutations21%–46%
BRCA2Somatic mutations2%
MSH3Somatic mutations22%–51%(34, 85, 86)
MSH6Somatic mutations9%–38%
MLH3Somatic mutations9%–28%
POLD3Somatic mutations37%(34, 85, 86)
Hepatocellular carcinomaNSB1Somatic mutations10%(87)
MSH2Promoter hypermethylation25%(88, 89)
Reduced protein expression18%
PMS2Promoter hypermethylation15%
MLH1Promoter hypermethylation8%
Reduced protein expression38%
Biliary tract cancerMSH2Loss of protein expression (IHC)7%(90, 91)
MSH6Loss of protein expression (IHC)7%
MLH1Loss of protein expression (IHC)1.5%
PMS2Loss of protein expression (IHC)1.5%
Prostate cancerBRCA2Homozygous deletion/heterozygous deletion/frameshift mutation14%(92, 93)
ATMFrameshift mutation12%
PALB2Frameshift mutation4%
CHK2Homozygous deletion4%
FANCAHomozygous deletion6%
BRCA1Homozygous deletion2%
MRE11Frameshift mutation2%
NSB1Frameshift mutation2%
MLH3Frameshift mutation4%(92, 93)
Endometrial cancerMLH1Promoter hypermethylation30%(7, 94)
POLESomatic mutations10%(7, 94)
Pancreatic cancerBRCA2Germline mutations1.5%(68, 95)
MSH2Loss of protein expression (IHC)15%(96)
MSH6Loss of protein expression (IHC)15%
MLH1Loss of protein expression (IHC)15%
PMS2Loss of protein expression (IHC)15%
  • NOTE: Genes in blue are related to DSBR, in green to MMR, in red to NER, in orange to nucleotide synthesis, and in gray to DNA replication. Genes marked with an asterisk refer to data reported in cell lines only. Mutations or alterations in genes related to cell cycle are described in Supplementary Table S2.

  • Abbreviations: DSBR, double-strand break repair; NER, nucleotide-excision repair; N.R., not reported.