Home LiteratureArticle Details
PMID: 25568919 Published · ppublish English Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Review

Hypermutation in human cancer genomes: footprints and mechanisms.

Nature reviews. Cancer ·Vol. 14 ·No. 12 ·2014-00-00 ·Pages 786-800

Roberts SA, Gordenin DA

Abstract

A role for somatic mutations in carcinogenesis is well accepted, but the degree to which mutation rates influence cancer initiation and development is under continuous debate. Recently accumulated genomic data have revealed that thousands of tumour samples are riddled by hypermutation, broadening support for the idea that many cancers acquire a mutator phenotype. This major expansion of cancer mutation data sets has provided unprecedented statistical power for the analysis of mutation spectra, which has confirmed several classical sources of mutation in cancer, highlighted new prominent mutation sources (such as apolipoprotein B mRNA editing enzyme catalytic polypeptide-like (APOBEC) enzymes) and empowered the search for cancer drivers. The confluence of cancer mutation genomics and mechanistic insight provides great promise for understanding the basic development of cancer through mutations.

MeSH Terms
DNA Damage DNA Repair Gene Dosage Genome, Human/genetics Humans Mutation Neoplasms/genetics
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Roberts Steven A
Gordenin Dmitry A
References (149)
149 references, click to expand
  1. Mutations arising during repair of chromosome breaks.
    Annu Rev Genet. 2012;46:455-73 PMID: 23146099
  2. APOBEC3G DNA deaminase acts processively 3' --> 5' on single-stranded DNA.
    Nat Struct Mol Biol. 2006 May;13(5):392-9 PMID: 16622407
  3. Somatic mutation hotspots correlate with DNA polymerase eta error spectrum.
    Nat Immunol. 2001 Jun;2(6):530-6 PMID: 11376340
  4. A time-invariant principle of genome evolution.
    Proc Natl Acad Sci U S A. 2010 Jul 20;107(29):13004-9 PMID: 20615949
  5. Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing.
    Cell. 2012 Sep 14;150(6):1107-20 PMID: 22980975
  6. Nonnegative matrix factorization: an analytical and interpretive tool in computational biology.
    PLoS Comput Biol. 2008;4(7):e1000029 PMID: 18654623
  7. A comprehensive catalogue of somatic mutations from a human cancer genome.
    Nature. 2010 Jan 14;463(7278):191-6 PMID: 20016485
  8. Human mutation rate associated with DNA replication timing.
    Nat Genet. 2009 Apr;41(4):393-5 PMID: 19287383
  9. APOBEC3B is an enzymatic source of mutation in breast cancer.
    Nature. 2013 Feb 21;494(7437):366-70 PMID: 23389445
  10. The relative roles in vivo of Saccharomyces cerevisiae Pol eta, Pol zeta, Rev1 protein and Pol32 in the bypass and mutation induction of an abasic site, T-T (6-4) photoadduct and T-T cis-syn cyclobutane dimer.
    Genetics. 2005 Feb;169(2):575-82 PMID: 15520252
  11. Cutting edge: DGYW/WRCH is a better predictor of mutability at G:C bases in Ig hypermutation than the widely accepted RGYW/WRCY motif and probably reflects a two-step activation-induced cytidine deaminase-triggered process.
    J Immunol. 2004 Mar 15;172(6):3382-4 PMID: 15004135
  12. Break-induced replication is highly inaccurate.
    PLoS Biol. 2011;9(2):e1000594 PMID: 21347245
  13. Somatic hypermutation: activation-induced deaminase for C/G followed by polymerase eta for A/T.
    J Exp Med. 2007 Jan 22;204(1):7-10 PMID: 17190841
  14. Splenic marginal zone lymphomas are characterized by loss of interstitial regions of chromosome 7q, 7q31.32 and 7q36.2 that include the protection of telomere 1 (POT1) and sonic hedgehog (SHH) genes.
    Br J Haematol. 2008 Jun;142(2):216-26 PMID: 18492102
  15. Similarities and differences between "uncapped" telomeres and DNA double-strand breaks.
    Chromosoma. 2012 Apr;121(2):117-30 PMID: 22203190
  16. Guanine holes are prominent targets for mutation in cancer and inherited disease.
    PLoS Genet. 2013;9(9):e1003816 PMID: 24086153
  17. Aristolochic acid-associated urothelial cancer in Taiwan.
    Proc Natl Acad Sci U S A. 2012 May 22;109(21):8241-6 PMID: 22493262
  18. Distribution and repair of photolesions in DNA: genetic consequences and the role of sequence context.
    Photochem Photobiol. 1993 Jan;57(1):163-74 PMID: 8389052
  19. Break-induced replication is a source of mutation clusters underlying kataegis.
    Cell Rep. 2014 Jun 12;7(5):1640-8 PMID: 24882007
  20. DNA deaminases induce break-associated mutation showers with implication of APOBEC3B and 3A in breast cancer kataegis.
    Elife. 2013;2:e00534 PMID: 23599896
  21. Division of labor at the eukaryotic replication fork.
    Mol Cell. 2008 Apr 25;30(2):137-44 PMID: 18439893
  22. Clustered mutations in yeast and in human cancers can arise from damaged long single-strand DNA regions.
    Mol Cell. 2012 May 25;46(4):424-35 PMID: 22607975
  23. Switching from high-fidelity replicases to low-fidelity lesion-bypass polymerases.
    Curr Opin Genet Dev. 2004 Apr;14(2):113-9 PMID: 15196456
  24. High-resolution characterization of a hepatocellular carcinoma genome.
    Nat Genet. 2011 May;43(5):464-9 PMID: 21499249
  25. Learning the parts of objects by non-negative matrix factorization.
    Nature. 1999 Oct 21;401(6755):788-91 PMID: 10548103
  26. Translesion DNA synthesis and mutagenesis in eukaryotes.
    Cold Spring Harb Perspect Biol. 2013 Mar;5(3):a012708 PMID: 23457261
  27. Damage-induced localized hypermutability.
    Cell Cycle. 2011 Apr 1;10(7):1073-85 PMID: 21406975
  28. Frequent POLE1 p.S297F mutation in Chinese patients with ovarian endometrioid carcinoma.
    Mutat Res. 2014 Mar;761:49-52 PMID: 24472300
  29. Chromatin organization is a major influence on regional mutation rates in human cancer cells.
    Nature. 2012 Aug 23;488(7412):504-7 PMID: 22820252
  30. A hypermutation phenotype and somatic MSH6 mutations in recurrent human malignant gliomas after alkylator chemotherapy.
    Cancer Res. 2006 Apr 15;66(8):3987-91 PMID: 16618716
  31. Oxidative stress-induced mutagenesis in single-strand DNA occurs primarily at cytosines and is DNA polymerase zeta-dependent only for adenines and guanines.
    Nucleic Acids Res. 2013 Oct;41(19):8995-9005 PMID: 23925127
  32. A small-cell lung cancer genome with complex signatures of tobacco exposure.
    Nature. 2010 Jan 14;463(7278):184-90 PMID: 20016488
  33. Aristolochic acids.
    Rep Carcinog. 2011;12:45-9 PMID: 21822318
  34. DNA base damage by reactive oxygen species, oxidizing agents, and UV radiation.
    Cold Spring Harb Perspect Biol. 2013 Feb;5(2). pii: a012559. doi: 10.1101/cshperspect.a012559 PMID: 23378590
  35. Increased mutagenesis and unique mutation signature associated with mitotic gene conversion.
    Science. 2010 Jul 2;329(5987):82-5 PMID: 20595613
  36. The biochemistry of somatic hypermutation.
    Annu Rev Immunol. 2008;26:481-511 PMID: 18304001
  37. Certain imidazotetrazines escape O6-methylguanine-DNA methyltransferase and mismatch repair.
    Oncology. 2011;80(3-4):195-207 PMID: 21720182
  38. Ultraviolet radiation accelerates BRAF-driven melanomagenesis by targeting TP53.
    Nature. 2014 Jul 24;511(7510):478-82 PMID: 24919155
  39. Fork reversal and ssDNA accumulation at stalled replication forks owing to checkpoint defects.
    Science. 2002 Jul 26;297(5581):599-602 PMID: 12142537
  40. Reduced local mutation density in regulatory DNA of cancer genomes is linked to DNA repair.
    Nat Biotechnol. 2014 Jan;32(1):71-5 PMID: 24336318
  41. Lack of recognition by global-genome nucleotide excision repair accounts for the high mutagenicity and persistence of aristolactam-DNA adducts.
    Nucleic Acids Res. 2012 Mar;40(6):2494-505 PMID: 22121226
  42. Rescuing stalled or damaged replication forks.
    Cold Spring Harb Perspect Biol. 2013 May;5(5):a012815 PMID: 23637285
  43. Discovery and saturation analysis of cancer genes across 21 tumour types.
    Nature. 2014 Jan 23;505(7484):495-501 PMID: 24390350
  44. Hypermutability of damaged single-strand DNA formed at double-strand breaks and uncapped telomeres in yeast Saccharomyces cerevisiae.
    PLoS Genet. 2008 Nov;4(11):e1000264 PMID: 19023402
  45. Hepatitis C virus induces a mutator phenotype: enhanced mutations of immunoglobulin and protooncogenes.
    Proc Natl Acad Sci U S A. 2004 Mar 23;101(12):4262-7 PMID: 14999097
  46. Functions and regulation of the APOBEC family of proteins.
    Semin Cell Dev Biol. 2012 May;23(3):258-68 PMID: 22001110
  47. The life history of 21 breast cancers.
    Cell. 2012 May 25;149(5):994-1007 PMID: 22608083
  48. Comprehensive molecular characterization of urothelial bladder carcinoma.
    Nature. 2014 Mar 20;507(7492):315-22 PMID: 24476821
  49. Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas.
    Nat Genet. 2013 Feb;45(2):136-44 PMID: 23263490
  50. A single-strand specific lesion drives MMS-induced hyper-mutability at a double-strand break in yeast.
    DNA Repair (Amst). 2010 Aug 5;9(8):914-21 PMID: 20663718
  51. Mismatch repair deficient human cells: spontaneous and MNNG-induced mutational spectra in the HPRT gene.
    Mutat Res. 2000 May 30;450(1-2):125-38 PMID: 10838138
  52. New insights into POLE and POLD1 germline mutations in familial colorectal cancer and polyposis.
    Hum Mol Genet. 2014 Jul 1;23(13):3506-12 PMID: 24501277
  53. Genotoxicity of tobacco smoke and tobacco smoke condensate: a review.
    Mutat Res. 2004 Nov;567(2-3):447-74 PMID: 15572290
  54. Patterns and processes of somatic mutations in nine major cancers.
    BMC Med Genomics. 2014;7:11 PMID: 24552141
  55. Heterogeneity of genomic evolution and mutational profiles in multiple myeloma.
    Nat Commun. 2014;5:2997 PMID: 24429703
  56. Evidence for mutation showers.
    Proc Natl Acad Sci U S A. 2007 May 15;104(20):8403-8 PMID: 17485671
  57. Reactions of oxyl radicals with DNA.
    Free Radic Biol Med. 1995 Jun;18(6):1033-77 PMID: 7628729
  58. Exome and whole-genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity.
    Nat Genet. 2013 May;45(5):478-86 PMID: 23525077
  59. Balancing AID and DNA repair during somatic hypermutation.
    Trends Immunol. 2009 Apr;30(4):173-81 PMID: 19303358
  60. Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia.
    Nature. 2011 Jul 7;475(7354):101-5 PMID: 21642962
  61. Functional uncoupling of twin polymerases: mechanism of polymerase dissociation from a lagging-strand block.
    J Biol Chem. 2004 May 14;279(20):21543-51 PMID: 15014081
  62. Somatic rearrangements across cancer reveal classes of samples with distinct patterns of DNA breakage and rearrangement-induced hypermutability.
    Genome Res. 2013 Feb;23(2):228-35 PMID: 23124520
  63. DNA deaminases AID and APOBEC3G act processively on single-stranded DNA.
    DNA Repair (Amst). 2007 Jun 1;6(6):689-92; author reply 693-4 PMID: 17291835
  64. Is there any genetic instability in human cancer?
    DNA Repair (Amst). 2010 Aug 5;9(8):858; discussion 859-60 PMID: 20605538
  65. Low fidelity DNA synthesis by human DNA polymerase-eta.
    Nature. 2000 Apr 27;404(6781):1011-3 PMID: 10801132
  66. Mutational heterogeneity in cancer and the search for new cancer-associated genes.
    Nature. 2013 Jul 11;499(7457):214-8 PMID: 23770567
  67. The role of gene body cytosine modifications in MGMT expression and sensitivity to temozolomide.
    Mol Cancer Ther. 2014 May;13(5):1334-44 PMID: 24568970
  68. The APOBEC3 family of retroelement restriction factors.
    Curr Top Microbiol Immunol. 2013;371:1-27 PMID: 23686230
  69. APOBEC-mediated cytosine deamination links PIK3CA helical domain mutations to human papillomavirus-driven tumor development.
    Cell Rep. 2014 Jun 26;7(6):1833-41 PMID: 24910434
  70. Analysis of TP53 mutation spectra reveals the fingerprint of the potent environmental carcinogen, aristolochic acid.
    Mutat Res. 2013 Jul-Sep;753(1):41-9 PMID: 23422071
  71. Multiple mechanisms control chromosome integrity after replication fork uncoupling and restart at irreparable UV lesions.
    Mol Cell. 2006 Jan 6;21(1):15-27 PMID: 16387650
  72. Error-free versus mutagenic processing of genomic uracil--relevance to cancer.
    DNA Repair (Amst). 2014 Jul;19:38-47 PMID: 24746924
  73. Clustered and genome-wide transient mutagenesis in human cancers: Hypermutation without permanent mutators or loss of fitness.
    Bioessays. 2014 Feb 26;:null PMID: 24615916
  74. Hypermutable non-synonymous sites are under stronger negative selection.
    PLoS Genet. 2008 Nov;4(11):e1000281 PMID: 19043566
  75. Deciphering signatures of mutational processes operative in human cancer.
    Cell Rep. 2013 Jan 31;3(1):246-59 PMID: 23318258
  76. The evolution of the unstable cancer genome.
    Curr Opin Genet Dev. 2014 Feb;24:61-7 PMID: 24657538
  77. In situ analyses of genome instability in breast cancer.
    Nat Genet. 2004 Sep;36(9):984-8 PMID: 15300252
  78. Melanoma genome sequencing reveals frequent PREX2 mutations.
    Nature. 2012 May 24;485(7399):502-6 PMID: 22622578
  79. Changes in the expression of telomere maintenance genes suggest global telomere dysfunction in B-chronic lymphocytic leukemia.
    Blood. 2008 Feb 15;111(4):2388-91 PMID: 18077792
  80. Evidence for APOBEC3B mutagenesis in multiple human cancers.
    Nat Genet. 2013 Sep;45(9):977-83 PMID: 23852168
  81. Whole-genome reconstruction and mutational signatures in gastric cancer.
    Genome Biol. 2012;13(12):R115 PMID: 23237666
  82. Comprehensive genomic characterization defines human glioblastoma genes and core pathways.
    Nature. 2008 Oct 23;455(7216):1061-8 PMID: 18772890
  83. The mutation spectrum revealed by paired genome sequences from a lung cancer patient.
    Nature. 2010 May 27;465(7297):473-7 PMID: 20505728
  84. Hypermutation of the inactive X chromosome is a frequent event in cancer.
    Cell. 2013 Oct 24;155(3):567-81 PMID: 24139898
  85. Novel mutagenic properties of abasic sites in Saccharomyces cerevisiae.
    J Mol Biol. 1995 Aug 11;251(2):229-36 PMID: 7643399
  86. Mutational signature of aristolochic acid exposure as revealed by whole-exome sequencing.
    Sci Transl Med. 2013 Aug 7;5(197):197ra102 PMID: 23926200
  87. Exome sequencing identifies a spectrum of mutation frequencies in advanced and lethal prostate cancers.
    Proc Natl Acad Sci U S A. 2011 Oct 11;108(41):17087-92 PMID: 21949389
  88. Microsatellite instability in colorectal cancer-the stable evidence.
    Nat Rev Clin Oncol. 2010 Mar;7(3):153-62 PMID: 20142816
  89. Epidemiology of doublet/multiplet mutations in lung cancers: evidence that a subset arises by chronocoordinate events.
    PLoS One. 2008;3(11):e3714 PMID: 19005564
  90. The choice of nucleotide inserted opposite abasic sites formed within chromosomal DNA reveals the polymerase activities participating in translesion DNA synthesis.
    DNA Repair (Amst). 2013 Nov;12(11):878-89 PMID: 23988736
  91. DNA damage response as an anti-cancer barrier: damage threshold and the concept of 'conditional haploinsufficiency'.
    Cell Cycle. 2007 Oct 1;6(19):2344-7 PMID: 17700066
  92. Differential relationship of DNA replication timing to different forms of human mutation and variation.
    Am J Hum Genet. 2012 Dec 7;91(6):1033-40 PMID: 23176822
  93. Signatures of mutational processes in human cancer.
    Nature. 2013 Aug 22;500(7463):415-21 PMID: 23945592
  94. Mutational processes molding the genomes of 21 breast cancers.
    Cell. 2012 May 25;149(5):979-93 PMID: 22608084
  95. The mechanisms of UV mutagenesis.
    J Radiat Res. 2011;52(2):115-25 PMID: 21436607
  96. R loops: from transcription byproducts to threats to genome stability.
    Mol Cell. 2012 Apr 27;46(2):115-24 PMID: 22541554
  97. Evidence of associations of APOBEC3B gene deletion with susceptibility to persistent HBV infection and hepatocellular carcinoma.
    Hum Mol Genet. 2013 Mar 15;22(6):1262-9 PMID: 23213177
  98. Hypermutation of multiple proto-oncogenes in B-cell diffuse large-cell lymphomas.
    Nature. 2001 Jul 19;412(6844):341-6 PMID: 11460166
  99. Mismatch repair and DNA damage signalling.
    DNA Repair (Amst). 2004 Aug-Sep;3(8-9):1091-101 PMID: 15279797
  100. Radiation.
    IARC Monogr Eval Carcinog Risks Hum. 2012;100(Pt D):7-303 PMID: 23189752
  101. Theoretical analysis of mutation hotspots and their DNA sequence context specificity.
    Mutat Res. 2003 Sep;544(1):65-85 PMID: 12888108
  102. Structure, function and evolution of CpG island promoters.
    Cell Mol Life Sci. 2003 Aug;60(8):1647-58 PMID: 14504655
  103. What does our genome encode?
    Genome Res. 2012 Sep;22(9):1602-11 PMID: 22955972
  104. Do mutator mutations fuel tumorigenesis?
    Cancer Metastasis Rev. 2013 Dec;32(3-4):353-61 PMID: 23592419
  105. Reply: Is There Any Genetic Instability in Human Cancer?
    DNA Repair (Amst). 2010 Aug 5;9(8):859-860 PMID: 20703319
  106. Oxidative DNA damage and disease: induction, repair and significance.
    Mutat Res. 2004 Sep;567(1):1-61 PMID: 15341901
  107. Mutational analysis reveals the origin and therapy-driven evolution of recurrent glioma.
    Science. 2014 Jan 10;343(6167):189-93 PMID: 24336570
  108. Punctuated evolution of prostate cancer genomes.
    Cell. 2013 Apr 25;153(3):666-77 PMID: 23622249
  109. Integrated genomic characterization of endometrial carcinoma.
    Nature. 2013 May 2;497(7447):67-73 PMID: 23636398
  110. DNA replication timing and higher-order nuclear organization determine single-nucleotide substitution patterns in cancer genomes.
    Nat Commun. 2013;4:1502 PMID: 23422670
  111. Tobacco smoke carcinogens, DNA damage and p53 mutations in smoking-associated cancers.
    Oncogene. 2002 Oct 21;21(48):7435-51 PMID: 12379884
  112. Population stratification of a common APOBEC gene deletion polymorphism.
    PLoS Genet. 2007 Apr 20;3(4):e63 PMID: 17447845
  113. Two mechanisms produce mutation hotspots at DNA breaks in Escherichia coli.
    Cell Rep. 2012 Oct 25;2(4):714-21 PMID: 23041320
  114. Mutation spectrum of copper-induced DNA damage.
    J Biol Chem. 1991 Apr 5;266(10):6401-6 PMID: 1826106
  115. Genome-wide mutational signatures of aristolochic acid and its application as a screening tool.
    Sci Transl Med. 2013 Aug 7;5(197):197ra101 PMID: 23926199
  116. Association of a germline copy number polymorphism of APOBEC3A and APOBEC3B with burden of putative APOBEC-dependent mutations in breast cancer.
    Nat Genet. 2014 May;46(5):487-91 PMID: 24728294
  117. APOBEC3 deletion polymorphism is associated with breast cancer risk among women of European ancestry.
    Carcinogenesis. 2013 Oct;34(10):2240-3 PMID: 23715497
  118. Identification of higher-order functional domains in the human ENCODE regions.
    Genome Res. 2007 Jun;17(6):917-27 PMID: 17568007
  119. Frequent somatic hypermutation of the 5' noncoding region of the BCL6 gene in B-cell lymphoma.
    Proc Natl Acad Sci U S A. 1995 Dec 19;92(26):12520-4 PMID: 8618933
  120. Mutagenesis by hydrogen peroxide treatment of mammalian cells: a molecular analysis.
    Carcinogenesis. 1990 Feb;11(2):283-93 PMID: 2302755
  121. Mutagenesis at methylated CpG sequences.
    Curr Top Microbiol Immunol. 2006;301:259-81 PMID: 16570852
  122. DNA replication timing.
    Cold Spring Harb Perspect Biol. 2013 Aug;5(8):a010132 PMID: 23838440
  123. Absolute quantification of somatic DNA alterations in human cancer.
    Nat Biotechnol. 2012 May;30(5):413-21 PMID: 22544022
  124. Germline and somatic polymerase ε and δ mutations define a new class of hypermutated colorectal and endometrial cancers.
    J Pathol. 2013 Jun;230(2):148-53 PMID: 23447401
  125. Break-induced replication repair of damaged forks induces genomic duplications in human cells.
    Science. 2014 Jan 3;343(6166):88-91 PMID: 24310611
  126. The landscape of microsatellite instability in colorectal and endometrial cancer genomes.
    Cell. 2013 Nov 7;155(4):858-68 PMID: 24209623
  127. Translesion synthesis DNA polymerases and control of genome stability.
    Front Biosci. 2006;11:2496-517 PMID: 16720328
  128. Base damage within single-strand DNA underlies in vivo hypermutability induced by a ubiquitous environmental agent.
    PLoS Genet. 2012;8(12):e1003149 PMID: 23271983
  129. Emerging landscape of oncogenic signatures across human cancers.
    Nat Genet. 2013 Oct;45(10):1127-33 PMID: 24071851
  130. Mutations induced by ultraviolet light.
    Mutat Res. 2005 Apr 1;571(1-2):19-31 PMID: 15748635
  131. An APOBEC cytidine deaminase mutagenesis pattern is widespread in human cancers.
    Nat Genet. 2013 Sep;45(9):970-6 PMID: 23852170
  132. Mechanisms of base substitution mutagenesis in cancer genomes.
    Genes (Basel). 2014 Mar 05;5(1):108-46 PMID: 24705290
  133. Genomic landscape of non-small cell lung cancer in smokers and never-smokers.
    Cell. 2012 Sep 14;150(6):1121-34 PMID: 22980976
  134. Loss of the mismatch repair protein MSH6 in human glioblastomas is associated with tumor progression during temozolomide treatment.
    Clin Cancer Res. 2007 Apr 1;13(7):2038-45 PMID: 17404084
  135. Aristolochic acid as a probable human cancer hazard in herbal remedies: a review.
    Mutagenesis. 2002 Jul;17(4):265-77 PMID: 12110620
  136. Uracil in DNA and its processing by different DNA glycosylases.
    Philos Trans R Soc Lond B Biol Sci. 2009 Mar 12;364(1517):563-8 PMID: 19008197
  137. MLH1-silenced and non-silenced subgroups of hypermutated colorectal carcinomas have distinct mutational landscapes.
    J Pathol. 2013 Jan;229(1):99-110 PMID: 22899370
  138. Exploring the genomes of cancer cells: progress and promise.
    Science. 2011 Mar 25;331(6024):1553-8 PMID: 21436442
  139. INDUCTION OF SPECIFIC MUTATIONS WITH 5-BROMOURACIL.
    Proc Natl Acad Sci U S A. 1958 Feb;44(2):112-9 PMID: 16590151
  140. The DNA damage response: making it safe to play with knives.
    Mol Cell. 2010 Oct 22;40(2):179-204 PMID: 20965415
  141. AID and somatic hypermutation.
    Adv Immunol. 2010;105:159-91 PMID: 20510733
  142. DNA end resection--unraveling the tail.
    DNA Repair (Amst). 2011 Mar 7;10(3):344-8 PMID: 21227759
  143. DNA mismatch repair.
    Annu Rev Biochem. 2005;74:681-710 PMID: 15952900
  144. Formation of DNA adducts and induction of lacI mutations in Big Blue Rat-2 cells treated with temozolomide: implications for the treatment of low-grade adult and pediatric brain tumors.
    Cancer Epidemiol Biomarkers Prev. 2003 Jun;12(6):545-51 PMID: 12815001
  145. Comprehensive molecular characterization of human colon and rectal cancer.
    Nature. 2012 Jul 19;487(7407):330-7 PMID: 22810696
  146. Migrating bubble during break-induced replication drives conservative DNA synthesis.
    Nature. 2013 Oct 17;502(7471):389-92 PMID: 24025772
  147. DNA replication fidelity.
    Annu Rev Biochem. 2000;69:497-529 PMID: 10966467
  148. Mutation signatures of carcinogen exposure: genome-wide detection and new opportunities for cancer prevention.
    Genome Med. 2014 Mar 31;6(3):24 PMID: 25031618
  149. A common deletion in the APOBEC3 genes and breast cancer risk.
    J Natl Cancer Inst. 2013 Apr 17;105(8):573-9 PMID: 23411593
Article Info
Journal
Nature reviews. Cancer
Abbr.
Nat Rev Cancer
ISSN
1474-1768
DOI
10.1038/nrc3816
Published
2014-00-00
Pages
786-800
Language
English
Region
England
NLM ID
101124168
PMCID
PMC4280484
Subset
IM
Grants
NIEHS NIH HHS · R00 ES022633 · United States
Intramural NIH HHS · Z99 ES999999 · United States
NIEHS NIH HHS · K99ES022633‑01 · United States
Corrections
ErratumIn
-
External Links
PubMed source DOI: 10.1038/nrc3816 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2