Clustered and genome-wide transient mutagenesis in human cancers: Hypermutation without permanent mutators or loss of fitness

BioEssays

Volumn 36, Issue 4, 2014, Pages 382-393

  Roberts, Steven A ^a   Gordenin, Dmitry A ^a  

^a NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES   (United States)

Author keywords

APOBEC; DNA damage; DNA repair; Hypermutation; Kataegis; Mutation cluster

Indexed keywords

ACTIVATION INDUCED CYTIDINE DEAMINASE; APOLIPOPROTEIN B MESSENGER RNA EDITING ENZYME CATALYTIC POLYPEPTIDE 1; DNA;

ARTICLE; CANCER GENETICS; DEAMINATION; DNA DAMAGE CHECKPOINT; ENZYMATIC DEGRADATION; ENZYME ACTIVATION; GENE CLUSTER; GENETIC ASSOCIATION; GENETIC CORRELATION; HUMAN; LOSS OF FUNCTION MUTATION; MALIGNANT TRANSFORMATION; MUTAGENESIS; PROTEIN EXPRESSION; SINGLE STRANDED DNA BREAK; SOMATIC HYPERMUTATION; YEAST;

EID: 84896728239     PISSN: 02659247     EISSN: 15211878     Source Type: Journal    
DOI: 10.1002/bies.201300140     Document Type: Article

References (120)

1. Campbell CD, Chong JX, Malig M, Ko A, et al. 2012. Estimating the human mutation rate using autozygosity in a founder population. Nat Genet 44: 1277-81.
2. Drake JW. 2007. Too many mutants with multiple mutations. Crit Rev Biochem Mol Biol 42: 247-58.
3. Burch LH, Yang Y, Sterling JF, Roberts SA, et al. 2011. Damage-induced localized hypermutability. Cell Cycle 10: 1073-85.
4. Fox EJ, Prindle MJ, Loeb LA. 2013. Do mutator mutations fuel tumorigenesis? Cancer Metastasis Rev 32: 353-61.
5. Loeb LA. 1991. Mutator phenotype may be required for multistage carcinogenesis. Cancer Res 51: 3075-9.
6. Alexandrov LB, Nik-Zainal S, Wedge DC, Aparicio SA, et al. 2013. Signatures of mutational processes in human cancer. Nature 500: 415-21.
7. Nik-Zainal S, Alexandrov LB, Wedge DC, Van Loo P, et al. 2012. Mutational processes molding the genomes of 21 breast cancers. Cell 149: 979-93.
8. Roberts SA, Sterling J, Thompson C, Harris S, et al. 2012. Clustered mutations in yeast and in human cancers can arise from damaged long single-strand DNA regions. Mol Cell 46: 424-35.
9. Thoma F. 2005. Repair of UV lesions in nucleosomes-intrinsic properties and remodeling. DNA Repair (Amst) 4: 855-69.
10. Rochette PJ, Brash DE. 2010. Human telomeres are hypersensitive to UV-induced DNA damage and refractory to repair. PLoS Genet 6: e1000926.
11. Gonzalez C, Hadany L, Ponder RG, Price M, et al. 2008. Mutability and importance of a hypermutable cell subpopulation that produces stress-induced mutants in Escherichia coli. PLoS Genet 4: e1000208.
12. Ponder RG, Fonville NC, Rosenberg SM. 2005. A switch from high-fidelity to error-prone DNA double-strand break repair underlies stress-induced mutation. Mol Cell 19: 791-804.
13. Holbeck SL, Strathern JN. 1997. A role for REV3 in mutagenesis during double-strand break repair in Saccharomyces cerevisiae. Genetics 147: 1017-24.
14. Rattray AJ, Shafer BK, McGill CB, Strathern JN. 2002. The roles of REV3 and RAD57 in double-strand-break-repair-induced mutagenesis of Saccharomyces cerevisiae. Genetics 162: 1063-77.
15. Strathern JN, Shafer BK, McGill CB. 1995. DNA synthesis errors associated with double-strand-break repair. Genetics 140: 965-72.
16. Malkova A, Haber JE. 2012. Mutations arising during repair of chromosome breaks. Annu Rev Genet 46: 455-73.
17. Hicks WM, Kim M, Haber JE. 2010. Increased mutagenesis and unique mutation signature associated with mitotic gene conversion. Science 329: 82-5.
18. Yang Y, Gordenin DA, Resnick MA. 2010. A single-strand specific lesion drives MMS-induced hyper-mutability at a double-strand break in yeast. DNA Repair 9: 914-21.
19. Yang Y, Sterling J, Storici F, Resnick MA, et al. 2008. Hypermutability of damaged single-strand DNA formed at double-strand breaks and uncapped telomeres in yeast Saccharomyces cerevisiae. PLoS Genet 4: e1000264.
20. Chan K, Sterling JF, Roberts SA, Bhagwat AS, et al. 2012. Base damage within single-strand DNA underlies in vivo hypermutability induced by a ubiquitous environmental agent. PLoS Genet 8: e1003149.
21. Liu M, Schatz DG. 2009. Balancing AID and DNA repair during somatic hypermutation. Trends Immunol 30: 173-81.
22. Peters A, Storb U. 1996. Somatic hypermutation of immunoglobulin genes is linked to transcription initiation. Immunity 4: 57-65.
23. Liu M, Duke JL, Richter DJ, Vinuesa CG, et al. 2008. Two levels of protection for the B cell genome during somatic hypermutation. Nature 451: 841-5.
24. Bransteitter R, Pham P, Scharff MD, Goodman MF. 2003. Activation-induced cytidine deaminase deaminates deoxycytidine on single-stranded DNA but requires the action of RNase. Proc Natl Acad Sci USA 100: 4102-7.
25. Dickerson SK, Market E, Besmer E, Papavasiliou FN. 2003. AID mediates hypermutation by deaminating single stranded DNA. J Exp Med 197: 1291-6.
26. Ramiro AR, Stavropoulos P, Jankovic M, Nussenzweig MC. 2003. Transcription enhances AID-mediated cytidine deamination by exposing single-stranded DNA on the nontemplate strand. Nat Immunol 4: 452-6.
27. Chaudhuri J, Tian M, Khuong C, Chua K, et al. 2003. Transcription-targeted DNA deamination by the AID antibody diversification enzyme. Nature 422: 726-30.
28. Yu K, Roy D, Bayramyan M, Haworth IS, et al. 2005. Fine-structure analysis of activation-induced deaminase accessibility to class switch region R-loops. Mol Cell Biol 25: 1730-6.
29. Wongsurawat T, Jenjaroenpun P, Kwoh CK, Kuznetsov V. 2012. Quantitative model of R-loop forming structures reveals a novel level of RNA-DNA interactome complexity. Nucleic Acids Res 40: e16.
30. Shen H. 2007. Activation-induced cytidine deaminase acts on double-strand breaks in vitro. Mol Immunol 44: 974-83.
31. Poltoratsky V, Heacock M, Kissling GE, Prasad R, et al. 2010. Mutagenesis dependent upon the combination of activation-induced deaminase expression and a double-strand break. Mol Immunol 48: 164-70.
32. Michael N, Shen HM, Longerich S, Kim N, et al. 2003. The E box motif CAGGTG enhances somatic hypermutation without enhancing transcription. Immunity 19: 235-42.
33. Xu Z, Fulop Z, Wu G, Pone EJ, et al. 2010. 14-3-3 adaptor proteins recruit AID to 5'-AGCT-3'-rich switch regions for class switch recombination. Nat Struct Mol Biol 17: 1124-35.
34. Chaudhuri J, Khuong C, Alt FW. 2004. Replication protein A interacts with AID to promote deamination of somatic hypermutation targets. Nature 430: 992-8.
35. Yamane A, Resch W, Kuo N, Kuchen S, et al. 2011. Deep-sequencing identification of the genomic targets of the cytidine deaminase AID and its cofactor RPA in B lymphocytes. Nat Immunol 12: 62-9.
36. Pavri R, Gazumyan A, Jankovic M, Di Virgilio M, et al. 2010. Activation-induced cytidine deaminase targets DNA at sites of RNA polymerase II stalling by interaction with Spt5. Cell 143: 122-33.
37. Willmann KL, Milosevic S, Pauklin S, Schmitz KM, et al. 2012. A role for the RNA pol II-associated PAF complex in AID-induced immune diversification. J Exp Med 209: 2099-111.
38. Basu U, Meng FL, Keim C, Grinstein V, et al. 2011. The RNA exosome targets the AID cytidine deaminase to both strands of transcribed duplex DNA substrates. Cell 144: 353-63.
39. Teng B, Burant CF, Davidson NO. 1993. Molecular cloning of an apolipoprotein B messenger RNA editing protein. Science 260: 1816-9.
40. Refsland EW, Harris RS. 2013. The APOBEC3 family of retroelement restriction factors. Curr Top Microbiol Immunol 371: 1-27.
41. Suspene R, Sommer P, Henry M, Ferris S, et al. 2004. APOBEC3G is a single-stranded DNA cytidine deaminase and functions independently of HIV reverse transcriptase. Nucleic Acids Rese 32: 2421-9.
42. Yu Q, Konig R, Pillai S, Chiles K, et al. 2004. Single-strand specificity of APOBEC3G accounts for minus-strand deamination of the HIV genome. Nat Struct Mol Biol 11: 435-42.
43. Love RP, Xu H, Chelico L. 2012. Biochemical analysis of hypermutation by the deoxycytidine deaminase APOBEC3A. J Biol Chem 287: 30812-22.
44. Harris RS, Petersen-Mahrt SK, Neuberger MS. 2002. RNA editing enzyme APOBEC1 and some of its homologs can act as DNA mutators. Mol Cell 10: 1247-53.
45. Suspene R, Aynaud MM, Guetard D, Henry M, et al. 2011. Somatic hypermutation of human mitochondrial and nuclear DNA by APOBEC3 cytidine deaminases, a pathway for DNA catabolism. Proc Natl Acad Sci USA 108: 4858-63.
46. Burns MB, Lackey L, Carpenter MA, Rathore A, et al. 2013. APOBEC3B is an enzymatic source of mutation in breast cancer. Nature 494: 366-70.
47. Westmoreland J, Ma W, Yan Y, Van Hulle K, et al. 2009. RAD50 is required for efficient initiation of resection and recombinational repair at random, gamma-induced double-strand break ends. PLoS Genet 5: e1000656.
48. Chung WH, Zhu Z, Papusha A, Malkova A, et al. 2010. Defective resection at DNA double-strand breaks leads to de novo telomere formation and enhances gene targeting. PLoS Genet 6: e1000948.
49. Wang J, Gonzalez KD, Scaringe WA, Tsai K, et al. 2007. Evidence for mutation showers. Proc Natl Acad Sci USA 104: 8403-8.
50. Roberts SA, Lawrence MS, Klimczak LJ, Grimm SA, et al. 2013. An APOBEC cytidine deaminase mutagenesis pattern is widespread in human cancers. Nat Genet 45: 970-6.
51. Mayorov VI, Rogozin IB, Adkison LR, Frahm C, et al. 2005. Expression of human AID in yeast induces mutations in context similar to the context of somatic hypermutation at G-C pairs in immunoglobulin genes. BMC Immunol 6: 10.
52. Rogozin IB, Pavlov YI. 2006. The cytidine deaminase AID exhibits similar functional properties in yeast and mammals. Mol Immunol 43: 1481-4.
53. Pham P, Bransteitter R, Petruska J, Goodman MF. 2003. Processive AID-catalysed cytosine deamination on single-stranded DNA simulates somatic hypermutation. Nature 424: 103-7.
54. Pavlov YI, Rogozin IB, Galkin AP, Aksenova AY, et al. 2002. Correlation of somatic hypermutation specificity and A-T base pair substitution errors by DNA polymerase eta during copying of a mouse immunoglobulin kappa light chain transgene. Proc Natl Acad Sci USA 99: 9954-9.
55. Rogozin IB, Pavlov YI, Bebenek K, Matsuda T, et al. 2001. Somatic mutation hotspots correlate with DNA polymerase eta error spectrum. Nat Immunol 2: 530-6.
56. Gibbs PE, McDonald J, Woodgate R, Lawrence CW. 2005. 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 169: 575-82.
57. Gibbs PE, Lawrence CW. 1995. Novel mutagenic properties of abasic sites in Saccharomyces cerevisiae. J Mol Biol 251: 229-36.
58. Simonelli V, Narciso L, Dogliotti E, Fortini P. 2005. Base excision repair intermediates are mutagenic in mammalian cells. Nucleic Acids Res 33: 4404-11.
59. Beale RC, Petersen-Mahrt SK, Watt IN, Harris RS, et al. 2004. Comparison of the differential context-dependence of DNA deamination by APOBEC enzymes: correlation with mutation spectra in vivo. J Mol Biol 337: 585-96.
60. Landry S, Narvaiza I, Linfesty DC, Weitzman MD. 2011. APOBEC3A can activate the DNA damage response and cause cell-cycle arrest. EMBO Rep 12: 444-50.
61. Petersen S, Casellas R, Reina-San-Martin B, Chen HT, et al. 2001. AID is required to initiate Nbs1/gamma-H2AX focus formation and mutations at sites of class switching. Nature 414: 660-5.
62. Chelico L, Pham P, Goodman MF. 2009. Mechanisms of APOBEC3G-catalyzed processive deamination of deoxycytidine on single-stranded DNA. Nat Struct Mol Biol 16: 454-5; author reply 5-6.
63. Chelico L, Pham P, Goodman MF. 2009. Stochastic properties of processive cytidine DNA deaminases AID and APOBEC3G. Philos Trans R Soc Lond B Biol Sci 364: 583-93.
64. Pham P, Chelico L, Goodman MF. 2007. DNA deaminases AID and APOBEC3G act processively on single-stranded DNA. DNA Repair (Amst) 6: 689-92; author reply 93-4.
65. Byeon IJ, Ahn J, Mitra M, Byeon CH, et al. 2013. NMR structure of human restriction factor APOBEC3A reveals substrate binding and enzyme specificity. Nat Commun 4: 1890.
66. Taylor BJ, Nik-Zainal S, Wu YL, Stebbings LA, et al. 2013. DNA deaminases induce break-associated mutation showers with implication of APOBEC3B and 3A in breast cancer kataegis. eLife 2: e00534.
67. Lada AG, Dhar A, Boissy RJ, Hirano M, et al. 2012. AID/APOBEC cytosine deaminase induces genome-wide kataegis. Biol Direct 7: 47; discussion 47.
68. Drier Y, Lawrence MS, Carter SL, Stewart C, et al. 2013. Somatic rearrangements across cancer reveal classes of samples with distinct patterns of DNA breakage and rearrangement-induced hypermutability. Genome Res 23: 228-35.
69. Lawrence MS, Stojanov P, Polak P, Kryukov GV, et al. 2013. Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature 499: 214-8.
70. Park S-R. 2012. Activation-induced cytidine deaminase in B cell immunity and cancers. Immune Network 12: 230.
71. Okazaki IM, Hiai H, Kakazu N, Yamada S, et al. 2003. Constitutive expression of AID leads to tumorigenesis. J Exp Med 197: 1173-81.
72. Takai A, Toyoshima T, Uemura M, Kitawaki Y, et al. 2009. A novel mouse model of hepatocarcinogenesis triggered by AID causing deleterious p53 mutations. Oncogene 28: 469-78.
73. Endo Y, Marusawa H, Chiba T. 2011. Involvement of activation-induced cytidine deaminase in the development of colitis-associated colorectal cancers. J Gastroenterol 46: 6-10.
74. Shinmura K, Igarashi H, Goto M, Tao H, et al. 2011. Aberrant expression and mutation-inducing activity of AID in human lung cancer. Ann Surg Oncol 18: 2084-92.
75. Kou T, Marusawa H, Kinoshita K, Endo Y, et al. 2007. Expression of activation-induced cytidine deaminase in human hepatocytes during hepatocarcinogenesis. Int J Cancer 120: 469-76.
76. Yamanaka S, Balestra ME, Ferrell LD, Fan J, et al. 1995. Apolipoprotein B mRNA-editing protein induces hepatocellular carcinoma and dysplasia in transgenic animals. Proc Natl Acad Sci USA 92: 8483-7.
77. Burns MB, Temiz NA, Harris RS. 2013. Evidence for APOBEC3B mutagenesis in multiple human cancers. Nat Genet 45: 977-83.
78. Komatsu A, Nagasaki K, Fujimori M, Amano J, et al. 2008. Identification of novel deletion polymorphisms in breast cancer. Int J Oncol 33: 261-70.
79. Xuan D, Li G, Cai Q, Deming-Halverson S, et al. 2013. APOBEC3 deletion polymorphism is associated with breast cancer risk among women of European ancestry. Carcinogenesis 34: 2240-3.
80. Long J, Delahanty RJ, Li G, Gao YT, et al. 2013. A common deletion in the APOBEC3 genes and breast cancer risk. J Natl Cancer Inst 105: 573-9.
81. Zhang T, Cai J, Chang J, Yu D, et al. 2013. Evidence of associations of APOBEC3B gene deletion with susceptibility to persistent HBV infection and hepatocellular carcinoma. Hum Mol Genet 22: 1262-9.
82. Zan H, Casali P. 2013. Regulation of Aicda expression and AID activity. Autoimmunity 46: 83-101.
83. de Yebenes VG, Belver L, Pisano DG, Gonzalez S, et al. 2008. miR-181b negatively regulates activation-induced cytidine deaminase in B cells. J Exp Med 205: 2199-206.
84. Dorsett Y, McBride KM, Jankovic M, Gazumyan A, et al. 2008. MicroRNA-155 suppresses activation-induced cytidine deaminase-mediated Myc-Igh translocation. Immunity 28: 630-8.
85. Teng G, Hakimpour P, Landgraf P, Rice A, et al. 2008. MicroRNA-155 is a negative regulator of activation-induced cytidine deaminase. Immunity 28: 621-9.
86. Uchimura Y, Barton LF, Rada C, Neuberger MS. 2011. REG-gamma associates with and modulates the abundance of nuclear activation-induced deaminase. J Exp Med 208: 2385-91.
87. McBride KM. 2004. Somatic hypermutation is limited by CRM1-dependent nuclear export of activation-induced deaminase. J Exp Med 199: 1235-44.
88. Ito S, Nagaoka H, Shinkura R, Begum N, et al. 2004. Activation-induced cytidine deaminase shuttles between nucleus and cytoplasm like apolipoprotein B mRNA editing catalytic polypeptide 1. Proc Natl Acad Sci USA 101: 1975-80.
89. Patenaude AM, Orthwein A, Hu Y, Campo VA, et al. 2009. Active nuclear import and cytoplasmic retention of activation-induced deaminase. Nat Struct Mol Biol 16: 517-27.
90. Basu U, Chaudhuri J, Alpert C, Dutt S, et al. 2005. The AID antibody diversification enzyme is regulated by protein kinase A phosphorylation. Nature 438: 508-11.
91. McBride KM, Gazumyan A, Woo EM, Schwickert TA, et al. 2008. Regulation of class switch recombination and somatic mutation by AID phosphorylation. J Exp Med 205: 2585-94.
92. Sun J, Keim CD, Wang J, Kazadi D, et al. 2013. E3-ubiquitin ligase Nedd4 determines the fate of AID-associated RNA polymerase II in B cells. Genes Dev 27: 1821-33.
93. Pauli E-K, Schmolke M, Hofmann H, Ehrhardt C, et al. 2009. High level expression of the anti-retroviral protein APOBEC3G is induced by influenza A virus but does not confer antiviral activity. Retrovirology 6: 38.
94. Komohara Y, Yano H, Shichijo S, Shimotohno K, et al. 2006. High expression of APOBEC3G in patients infected with hepatitis C virus. J Mol Histol 37: 327-32.
95. Stenglein MD, Burns MB, Li M, Lengyel J, et al. 2010. APOBEC3 proteins mediate the clearance of foreign DNA from human cells. Nat Struct Mol Biol 17: 222-9.
96. Zhou L, Wang X, Wang YJ, Zhou Y, et al. 2009. Activation of toll-like receptor-3 induces interferon-lambda expression in human neuronal cells. Neuroscience 159: 629-37.
97. Stopak KS, Chiu YL, Kropp J, Grant RM, et al. 2007. Distinct patterns of cytokine regulation of APOBEC3G expression and activity in primary lymphocytes, macrophages, and dendritic cells. J Biol Chem 282: 3539-46.
98. Vazquez N, Schmeisser H, Dolan MA, Bekisz J, et al. 2011. Structural variants of IFNalpha preferentially promote antiviral functions. Blood 118: 2567-77.
99. Tanaka Y, Marusawa H, Seno H, Matsumoto Y, et al. 2006. Anti-viral protein APOBEC3G is induced by interferon-alpha stimulation in human hepatocytes. Biochem Biophys Res Commun 341: 314-9.
100. Menendez D, Nguyen TA, Freudenberg JM, Mathew VJ, et al. 2013. Diverse stresses dramatically alter genome-wide p53 binding and transactivation landscape in human cancer cells. Nucleic Acids Res 41: 7286-301.
101. Pauklin S, Sernandez IV, Bachmann G, Ramiro AR, et al. 2009. Estrogen directly activates AID transcription and function. J Exp Med 206: 99-111.
102. Bogerd HP, Wiegand HL, Hulme AE, Garcia-Perez JL, et al. 2006. Cellular inhibitors of long interspersed element 1 and Alu retrotransposition. Proc Natl Acad Sci USA 103: 8780-5.
103. Lackey L, Demorest ZL, Land AM, Hultquist JF, et al. 2012. APOBEC3B and AID have similar nuclear import mechanisms. J Mol Biol 419: 301-14.
104. Aynaud MM, Suspene R, Vidalain PO, Mussil B, et al. 2012. Human Tribbles 3 protects nuclear DNA from cytidine deamination by APOBEC3A. J Biol Chem 287: 39182-92.
105. Mehta A, Kinter MT, Sherman NE, Driscoll DM. 2000. Molecular cloning of apobec-1 complementation factor, a novel RNA-binding protein involved in the editing of apolipoprotein B mRNA. Mol Cell Biol 20: 1846-54.
106. Chester A, Weinreb V, Carter CW, Jr., Navaratnam N. 2004. Optimization of apolipoprotein B mRNA editing by APOBEC1 apoenzyme and the role of its auxiliary factor, ACF. RNA 10: 1399-411.
107. Chiba T, Marusawa H. 2009. A novel mechanism for inflammation-associated carcinogenesis; an important role of activation-induced cytidine deaminase (AID) in mutation induction. J Mol Med (Berl) 87: 1023-7.
108. Saini N, Ramakrishnan S, Elango R, Ayyar S, et al. 2013. Migrating bubble during break-induced replication drives conservative DNA synthesis. Nature 502: 389-92.
109. Lada AG, Waisertreiger IS, Grabow CE, Prakash A, et al. 2011. Replication protein A (RPA) hampers the processive action of APOBEC3G cytosine deaminase on single-stranded DNA. PLoS One 6: e24848.
110. Di Micco R, Fumagalli M, Cicalese A, Piccinin S, et al. 2006. Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replication. Nature 444: 638-42.
111. Bartkova J, Rezaei N, Liontos M, Karakaidos P, et al. 2006. Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints. Nature 444: 633-7.
112. Halazonetis TD, Gorgoulis VG, Bartek J. 2008. An oncogene-induced DNA damage model for cancer development. Science 319: 1352-5.
113. Neelsen KJ, Zanini IM, Herrador R, Lopes M. 2013. Oncogenes induce genotoxic stress by mitotic processing of unusual replication intermediates. J Cell Biol 200: 699-708.
114. Jones RM, Mortusewicz O, Afzal I, Lorvellec M, et al. 2013. Increased replication initiation and conflicts with transcription underlie Cyclin E-induced replication stress. Oncogene 32: 3744-53.
115. Nik-Zainal S, Van Loo P, Wedge DC, Alexandrov LB, et al. 2012. The life history of 21 breast cancers. Cell 149: 994-1007.
116. Reddy JP, Peddibhotla S, Bu W, Zhao J, et al. 2010. Defining the ATM-mediated barrier to tumorigenesis in somatic mammary cells following ErbB2 activation. Proc Natl Acad Sci USA 107: 3728-33.
117. Camps M, Herman A, Loh E, Loeb LA. 2007. Genetic constraints on protein evolution. Crit Rev Biochem Mol Biol 42: 313-26.
118. Frankel N, Erezyilmaz DF, McGregor AP, Wang S, et al. 2011. Morphological evolution caused by many subtle-effect substitutions in regulatory DNA. Nature 474: 598-603.
119. Thielen BK, McNevin JP, McElrath MJ, Hunt BV, et al. 2010. Innate immune signaling induces high levels of TC-specific deaminase activity in primary monocyte-derived cells through expression of APOBEC3A isoforms. J Biol Chem 285: 27753-66.
120. Carter SL, Cibulskis K, Helman E, McKenna A, et al. 2012. Absolute quantification of somatic DNA alterations in human cancer. Nat Biotechnol 30: 413-21.