TP53 mutations in human cancer: Database reassessment and prospects for the next decade

Human Mutation

Volumn 35, Issue 6, 2014, Pages 672-688

  Leroy, Bernard ^a   Anderson, Martha ^b   Soussi, Thierry ^a,b  

^a SORBONNE UNIVERSITÉ   (France)

^b KAROLINSKA INSTITUTE   (Sweden)

Author keywords

Cancer; LSDB; Mutation; TP53

Indexed keywords

CPG OLIGODEOXYNUCLEOTIDE; PROTEIN P53; TP53 PROTEIN, HUMAN;

FRAMESHIFT MUTATION; GENE FREQUENCY; GENE MUTATION; GENETIC HETEROGENEITY; GENETIC VARIABILITY; GENOME; HIGH THROUGHPUT SEQUENCING; HUMAN; OLIGOMERIZATION; PLEIOTROPY; PRIORITY JOURNAL; PROTEIN PROCESSING; REVIEW; GENETIC DATABASE; GENETICS; GERMLINE MUTATION; NEOPLASM; NUCLEOTIDE SEQUENCE; PATHOLOGY;

DATABASES, GENETIC; DNA MUTATIONAL ANALYSIS; GERM-LINE MUTATION; HUMANS; NEOPLASMS; TUMOR SUPPRESSOR PROTEIN P53;

EID: 84901054744     PISSN: 10597794     EISSN: 10981004     Source Type: Journal    
DOI: 10.1002/humu.22552     Document Type: Review

References (124)

1. Alexandrov LB, Nik-Zainal S, Wedge DC, Aparicio SA, Behjati S, Biankin AV, Bignell GR, Bolli N, Borg A, Borresen-Dale AL, Boyault S, Burkhardt B, et al. 2013a. Signatures of mutational processes in human cancer. Nature 500:415-421.
2. Alexandrov LB, Nik-Zainal S, Wedge DC, Campbell PJ, Stratton MR. 2013b. Deciphering signatures of mutational processes operative in human cancer. Cell Rep 3:246-259.
3. Aylon Y, Oren M. 2011. New plays in the p53 theater. Curr Opin Genet Dev 21:86-92.
4. Baker SJ, Fearon ER, Nigro JM, Hamilton SR, Preisinger AC, Jessup JM, vanTuinen P, Ledbetter DH, Barker DF, Nakamura Y, White R, Vogelstein B. 1989. Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas. Science 244:217-221.
5. Barretina J, Taylor BS, Banerji S, Ramos AH, Lagos-Quintana M, Decarolis PL, Shah K, Socci ND, Weir BA, Ho A, Chiang DY, Reva B, et al. 2010. Subtype-specific genomic alterations define new targets for soft-tissue sarcoma therapy. Nat Genet 42:715-721.
6. Bell D, Berchuck A, Birrer M, Chien J, Cramer DW, Dao F, Dhir R, Disaia P, Gabra H, Glenn P, Godwin AK, Gross J, et al. 2011. Integrated genomic analyses of ovarian carcinoma. Nature 474:609-615.
7. Berglind H, Pawitan Y, Kato S, Ishioka C, Soussi T. 2008. Analysis of p53 mutation status in human cancer cell lines: a paradigm for cell line cross-contamination. Cancer Biol Ther 7:699-708.
8. Berkers CR, Maddocks OD, Cheung EC, Mor I, Vousden KH. 2013. Metabolic regulation by p53 family members. Cell Metab 18:617-633.
9. Blandino G, Levine AJ, Oren M. 1999. Mutant p53 gain of function: differential effects of different p53 mutants on resistance of cultured cells to chemotherapy. Oncogene 18:477-485.
10. Boffetta P. 2010. Biomarkers in cancer epidemiology: an integrative approach. Carcinogenesis 31:121-126.
11. Brady CA, Jiang D, Mello SS, Johnson TM, Jarvis LA, Kozak MM, Kenzelmann Broz D, Basak S, Park EJ, McLaughlin ME, Karnezis AN, Attardi LD. 2011. Distinct p53 transcriptional programs dictate acute DNA-damage responses and tumor suppression. Cell 145:571-583.
12. Brash DE. 1997. Sunlight and the onset of skin cancer. Trends Genet 13:410-414.
13. Burns MB, Lackey L, Carpenter MA, Rathore A, Land AM, Leonard B, Refsland EW, Kotandeniya D, Tretyakova N, Nikas JB, Yee D, Temiz NA, et al. 2013. APOBEC3B is an enzymatic source of mutation in breast cancer. Nature 494:366-370.
14. Caron de Fromentel C, Soussi T. 1992. TP53 tumor suppressor gene: a model for investigating human mutagenesis. Genes Chromosomes Cancer 4:1-15.
15. Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA, Jacobsen A, Byrne CJ, Heuer ML, Larsson E, Antipin Y, Reva B, et al. 2012. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov 2:401-404.
16. Chin L, Hahn WC, Getz G, Meyerson M. 2011. Making sense of cancer genomic data. Genes Dev 25:534-555.
17. Cho Y, Gorina S, Jeffrey PD, Pavletich NP. 1994. Crystal structure of a p53 tumor suppressor-DNA complex: understanding tumorigenic mutations. Science 265:346-355.
18. Ciriello G, Cerami E, Sander C, Schultz N. 2012. Mutual exclusivity analysis identifies oncogenic network modules. Genome Res 22:398-406.
19. CLCG Project. 2013. A genomics-based classification of human lung tumors. Sci Transl Med 5:209ra153.
20. Clore GM, Ernst J, Clubb R, Omichinski JG, Kennedy WM, Sakaguchi K, Appella E, Gronenborn AM. 1995. Refined solution structure of the oligomerization domain of the tumour suppressor p53. Nat Struct Biol 2:321-333.
21. Clore GM, Omichinski JG, Sakaguchi K, Zambrano N, Sakamoto H, Appella E, Gronenborn AM. 1994. High-resolution structure of the oligomerization domain of p53 by multidimensional NMR. Science 265:386-391.
22. Cooper DN, Youssoufian H. 1988. The CpG dinucleotide and human genetic disease. Hum Genet 78:151-155.
23. Cooper WA, Lam DC, O'Toole SA, Minna JD. 2013. Molecular biology of lung cancer. J Thorac Dis 5(Suppl 5):S479-S490.
24. Crotti LB, Horowitz DS. 2009. Exon sequences at the splice junctions affect splicing fidelity and alternative splicing. Proc Natl Acad Sci USA 106:18954-18959.
25. Curtis C, Shah SP, Chin SF, Turashvili G, Rueda OM, Dunning MJ, Speed D, Lynch AG, Samarajiwa S, Yuan Y, Graf S, Ha G, et al. 2012. The genomic and transcriptomic architecture of 2, 000 breast tumours reveals novel subgroups. Nature 486:346-352.
26. Custodio G, Parise GA, Kiesel Filho N, Komechen H, Sabbaga CC, Rosati R, Grisa L, Parise IZ, Pianovski MA, Fiori CM, Ledesma JA, Barbosa JR, et al. 2013. Impact of neonatal screening and surveillance for the TP53 R337H mutation on early detection of childhood adrenocortical tumors. J Clin Oncol 31:2619-2626.
27. Dawson SJ, Tsui DW, Murtaza M, Biggs H, Rueda OM, Chin SF, Dunning MJ, Gale D, Forshew T, Mahler-Araujo B, Rajan S, Humphray S, et al. 2013. Analysis of circulating tumor DNA to monitor metastatic breast cancer. N Engl J Med 368:1199-1209.
28. Denissenko MF, Chen JX, Tang MS, Pfeifer GP. 1997. Cytosine methylation determines hot spots of DNA damage in the human P53 gene. Proc Natl Acad Sci USA 94:3893-3898.
29. Diehl F, Li M, Dressman D, He Y, Shen D, Szabo S, Diaz LAJ, Goodman SN, David KA, Juhl H, Kinzler KW, Vogelstein B. 2005. Detection and quantification of mutations in the plasma of patients with colorectal tumors. Proc Natl Acad Sci USA 102:16368-16373.
30. DiGiammarino EL, Lee AS, Cadwell C, Zhang W, Bothner B, Ribeiro RC, Zambetti G, Kriwacki RW. 2002. A novel mechanism of tumorigenesis involving pH-dependent destabilization of a mutant p53 tetramer. Nat Struct Biol 9:12-16.
31. Donehower LA. 2014. Insights into wild-type and mutant p53 functions provided by genetically engineered mice. Hum Mutat 35:715-727.
32. Dumay A, Feugeas JP, Wittmer E, Lehmann-Che J, Bertheau P, Espie M, Plassa LF, Cottu P, Marty M, Andre F, Sotiriou C, Pusztai L, et al. 2013. Distinct tumor protein p53 mutants in breast cancer subgroups. Int J Cancer 132:1227-1231.
33. Edlund K, Larsson O, Ameur A, Bunikis I, Gyllensten U, Leroy B, Sundstrom M, Micke P, Botling J, Soussi T. 2012. Data-driven unbiased curation of the TP53 tumor suppressor gene mutation database and validation by ultradeep sequencing of human tumors. Proc Natl Acad Sci USA 109:9551-9556.
34. Gaglia G, Guan Y, Shah JV, Lahav G. 2013. Activation and control of p53 tetramerization in individual living cells. Proc Natl Acad Sci USA 110:15497-15501.
35. Gao J, Aksoy BA, Dogrusoz U, Dresdner G, Gross B, Sumer SO, Sun Y, Jacobsen A, Sinha R, Larsson E, Cerami E, Sander C, et al. 2013. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal 6:pl1.
36. Giglia-Mari G, Sarasin A. 2003. TP53 mutations in human skin cancers. Hum Mutat 21:217-228.
37. Grollman AP, Shibutani S, Moriya M, Miller F, Wu L, Moll U, Suzuki N, Fernandes A, Rosenquist T, Medverec Z, Jakovina K, Brdar B, et al. 2007. Aristolochic acid and the etiology of endemic (Balkan) nephropathy. Proc Natl Acad Sci USA 104:12129-12134.
38. Gupta A. 2013. Fraud and misconduct in clinical research: a concern. Perspect Clin Res 4:144-147.
39. Hartmann A, Blaszyk H, Kovach JS, Sommer SS. 1997. The molecular epidemiology of p53 gene mutations in human breast cancer. Trends Genet 13:27-33.
40. He L, He X, Lowe SW, Hannon GJ. 2007. microRNAs join the p53 network-another piece in the tumour-suppression puzzle. Nat Rev Cancer 7:819-822.
41. Hermeking H. 2012. MicroRNAs in the p53 network: micromanagement of tumour suppression. Nat Rev Cancer 12:613-626.
42. Hoang ML, Chen CH, Sidorenko VS, He J, Dickman KG, Yun BH, Moriya M, Niknafs N, Douville C, Karchin R, Turesky RJ, Pu YS, et al. 2013. Mutational signature of aristolochic acid exposure as revealed by whole-exome sequencing. Sci Transl Med 5:197ra102.
43. Hollstein M, Sidransky D, Vogelstein B, Harris CC. 1991. p53 mutations in human cancers. Science 253:49-53.
44. Hong B, van den Heuvel AP, Prabhu VV, Zhang S, El-Deiry WS. 2014. Targeting tumor suppressor p53 for cancer therapy: strategies, challenges and opportunities. Curr Drug Targets 15:80-89.
45. Hussain SP, Schwank J, Staib F, Wang XW, Harris CC. 2007. TP53 mutations and hepatocellular carcinoma: insights into the etiology and pathogenesis of liver cancer. Oncogene 26:2166-2176.
46. Hutchinson L, DeVita VTJ. 2009. The Holy Grail of biomarkers. Nat Rev Clin Oncol 6:553.
47. Kamada R, Nomura T, Anderson CW, Sakaguchi K. 2011. Cancer-associated p53 tetramerization domain mutants: quantitative analysis reveals a low threshold for tumor suppressor inactivation. J Biol Chem 286:252-258.
48. Kamihara J, Rana HQ, Garber JE. 2014. Germline TP53 mutations and the changing landscape of Li-Fraumeni syndrome. Hum Mutat 35:654-662.
49. Kandoth C, McLellan MD, Vandin F, Ye K, Niu B, Lu C, Xie M, Zhang Q, McMichael JF, Wyczalkowski MA, Leiserson MD, Miller CA, et al. 2013. Mutational landscape and significance across 12 major cancer types. Nature 502:333-339.
50. Kato S, Han SY, Liu W, Otsuka K, Shibata H, Kanamaru R, Ishioka C. 2003. Understanding the function-structure and function-mutation relationships of p53 tumor suppressor protein by high-resolution missense mutation analysis. Proc Natl Acad Sci USA 100:8424-8429.
51. Kawaguchi T, Kato S, Otsuka K, Watanabe G, Kumabe T, Tominaga T, Yoshimoto T, Ishioka C. 2005. The relationship among p53 oligomer formation, structure and transcriptional activity using a comprehensive missense mutation library. Oncogene 24:6976-6981.
52. Khoury MP, Bourdon JC. 2010. The isoforms of the p53 protein. Cold Spring Harb Perspect Biol 2:a000927.
53. Kress M, May E, Cassingena R, May P. 1979. Simian virus 40-transformed cells express new species of proteins precipitable by anti-simian virus 40 tumor serum. J Virol 31:472-483.
54. Kussie PH, Gorina S, Marechal V, Elenbaas B, Moreau J, Levine AJ, Pavletich NP. 1996. Structure of the MDM2 oncoprotein bound to the p53 tumor suppressor transactivation domain. Science 274:948-953.
55. Lane DP, Cheok CF, Lain S. 2010. p53-based cancer therapy. Cold Spring Harb Perspect Biol 2:a001222.
56. Lane DP, Crawford LV. 1979. T antigen is bound to a host protein in SV40-transformed cells. Nature 278:261-263.
57. Laurie NA, Donovan SL, Shih CS, Zhang J, Mills N, Fuller C, Teunisse A, Lam S, Ramos Y, Mohan A, Johnson D, Wilson M, et al. 2006. Inactivation of the p53 pathway in retinoblastoma. Nature 444:61-66.
58. Lawrence MS, Stojanov P, Polak P, Kryukov GV, Cibulskis K, Sivachenko A, Carter SL, Stewart C, Mermel CH, Roberts SA, Kiezun A, Hammerman PS, et al. 2013. Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature 499:214-218.
59. Lehmann S, Bykov VJ, Ali D, Andren O, Cherif H, Tidefelt U, Uggla B, Yachnin J, Juliusson G, Moshfegh A, Paul C, Wiman KG, et al. 2012. Targeting p53 in vivo: a first-in-human study with p53-targeting compound APR-246 in refractory hematologic malignancies and prostate cancer. J Clin Oncol 30:3633-3639.
60. Leroy B, Girard L, Minna JD, Gazdar AF, Soussi T. 2014. Analysis of p53 mutation status in human cancer cell lines: a reassessment. Hum Mutat 35:756-765.
61. Letouze E, Rosati R, Komechen H, Doghman M, Marisa L, Fluck C, de Krijger RR, van Noesel MM, Mas JC, Pianovski MA, Zambetti GP, Figueiredo BC, et al. 2012. SNP array profiling of childhood adrenocortical tumors reveals distinct pathways of tumorigenesis and highlights candidate driver genes. J Clin Endocrinol Metab 97:E1284-E1293.
62. Levine AJ. 2009. The common mechanisms of transformation by the small DNA tumor viruses: the inactivation of tumor suppressor gene products: p53. Virology 384:285-293.
63. Levine AJ, Tomasini R, McKeon FD, Mak TW, Melino G. 2011. The p53 family: guardians of maternal reproduction. Nat Rev Mol Cell Biol 12:259-265.
64. Li J, Poi MJ, Tsai MD. 2011. Regulatory mechanisms of tumor suppressor P16(INK4A) and their relevance to cancer. Biochemistry 50:5566-5582.
65. Li T, Kon N, Jiang L, Tan M, Ludwig T, Zhao Y, Baer R, Gu W. 2012. Tumor suppression in the absence of p53-mediated cell-cycle arrest, apoptosis, and senescence. Cell 149:1269-1283.
66. Linzer DI, Levine AJ. 1979. Characterization of a 54K dalton cellular SV40 tumor antigen present in SV40-transformed cells and uninfected embryonal carcinoma cells. Cell 17:43-52.
67. Malcikova J, Pavlova S, Kozubik KS, Pospisilova S. 2014. TP53 mutation analysis in clinical practice: lessons from chronic lymphocytic leukemia. Hum Mutat 35:663-671.
68. Masuda H, Miller C, Koeffler HP, Battifora H, Cline MJ. 1987. Rearrangement of the p53 gene in human osteogenic sarcomas. Proc Natl Acad Sci USA 84:7716-7719.
69. Meek DW, Anderson CW. 2009. Posttranslational modification of p53: cooperative integrators of function. Cold Spring Harb Perspect Biol 1:a000950.
70. Moody CA, Laimins LA. 2010. Human papillomavirus oncoproteins: pathways to transformation. Nat Rev Cancer 10:550-560.
71. Natan E, Hirschberg D, Morgner N, Robinson CV, Fersht AR. 2009. Ultraslow oligomerization equilibria of p53 and its implications. Proc Natl Acad Sci USA 106:14327-14332.
72. Ng PC, Henikoff S. 2006. Predicting the effects of amino acid substitutions on protein function. Annu Rev Genomics Hum Genet 7:61-80.
73. Nguyen TA, Menendez D, Resnick MA, Anderson CW. 2014. Mutant TP53 posttranslational modifications: challenges and opportunities. Hum Mutat 35:738-755.
74. Ogino S, Fuchs CS, Giovannucci E. 2012. How many molecular subtypes? Implications of the unique tumor principle in personalized medicine. Expert Rev Mol Diagn 12:621-628.
75. Oliner JD, Pietenpol JA, Thiagalingam S, Gyuris J, Kinzler KW, Vogelstein B. 1993. Oncoprotein MDM2 conceals the activation domain of tumour suppressor p53. Nature 362:857-860.
76. Olsson A, Manzl C, Strasser A, Villunger A. 2007. How important are post-translational modifications in p53 for selectivity in target-gene transcription and tumour suppression? Cell Death Differ 14:1561-1575.
77. Ory K, Legros Y, Auguin C, Soussi T. 1994. Analysis of the most representative tumour-derived p53 mutants reveals that changes in protein conformation are not correlated with loss of transactivation or inhibition of cell proliferation. EMBO J 13:3496-3504.
78. Ozturk M. 1991. p53 mutation in hepatocellular carcinoma after aflatoxin exposure. Lancet 338:1356-1359.
79. Pleasance ED, Stephens PJ, O'Meara S, McBride DJ, Meynert A, Jones D, Lin ML, Beare D, Lau KW, Greenman C, Varela I, Nik-Zainal S, et al. 2010. A small-cell lung cancer genome with complex signatures of tobacco exposure. Nature 463:184-190.
80. Poon SL, Pang ST, McPherson JR, Yu W, Huang KK, Guan P, Weng WH, Siew EY, Liu Y, Heng HL, Chong SC, Gan A, et al. 2013. Genome-wide mutational signatures of aristolochic acid and its application as a screening tool. Sci Transl Med 5:197ra101.
81. Pugh TJ, Weeraratne SD, Archer TC, Pomeranz Krummel DA, Auclair D, Bochicchio J, Carneiro MO, Carter SL, Cibulskis K, Erlich RL, Greulich H, Lawrence MS, et al. 2012. Comprehensive molecular characterization of human colon and rectal cancer. Nature 487:330-337.
82. Rajagopalan S, Huang F, Fersht AR. 2011. Single-molecule characterization of oligomerization kinetics and equilibria of the tumor suppressor p53. Nucleic Acids Res 39:2294-2303.
83. Reva B, Antipin Y, Sander C. 2011. Predicting the functional impact of protein mutations: application to cancer genomics. Nucleic Acids Res 39:e118.
84. Ribeiro RC, Sandrini F, Figueiredo B, Zambetti GP, Michalkiewicz E, Lafferty AR, DeLacerda L, Rabin M, Cadwell C, Sampaio G, Cat I, Stratakis CA, et al. 2001. An inherited p53 mutation that contributes in a tissue-specific manner to pediatric adrenal cortical carcinoma. Proc Natl Acad Sci USA 98:9330-9335.
85. Roberts SA, Lawrence MS, Klimczak LJ, Grimm SA, Fargo D, Stojanov P, Kiezun A, Kryukov GV, Carter SL, Saksena G, Harris S, Shah RR, et al. 2013. An APOBEC cytidine deaminase mutagenesis pattern is widespread in human cancers. Nat Genet 45:970-976.
86. Rodenhuis S, Slebos RJ, Boot AJ, Evers SG, Mooi WJ, Wagenaar SS, van Bodegom PC, Bos JL. 1988. Incidence and possible clinical significance of K-ras oncogene activation in adenocarcinoma of the human lung. Cancer Res 48:5738-5741.
87. Saller E, Tom E, Brunori M, Otter M, Estreicher A, Mack DH, Iggo R. 1999. Increased apoptosis induction by 121F mutant p53. EMBO J 18:4424-4437.
88. Sauna ZE, Kimchi-Sarfaty C. 2011. Understanding the contribution of synonymous mutations to human disease. Nat Rev Genet 12:683-691.
89. Scheffner M, Werness BA, Huibregtse JM, Levine AJ, Howley PM. 1990. The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell 63:1129-1136.
90. Schetter AJ, Harris CC. 2012. Tumor suppressor p53 (TP53) at the crossroads of the exposome and the cancer genome. Proc Natl Acad Sci USA 109:7955-7956.
91. Schlomm T, Iwers L, Kirstein P, Jessen B, Kollermann J, Minner S, Passow-Drolet A, Mirlacher M, Milde-Langosch K, Graefen M, Haese A, Steuber T, et al. 2008. Clinical significance of p53 alterations in surgically treated prostate cancers. Mod Pathol 21:1371-1378.
92. Selivanova G. 2010. Therapeutic targeting of p53 by small molecules. Semin Cancer Biol 20:46-56.
93. Slade N, Moll UM, Brdar B, Zoric A, Jelakovic B. 2009. p53 mutations as fingerprints for aristolochic acid: an environmental carcinogen in endemic (Balkan) nephropathy. Mutat Res 663:1-6.
94. Soussi T. 2011a. TP53 mutations in human cancer: database reassessment and prospects for the next decade. Adv Cancer Res 110:107-139.
95. Soussi T. 2011b. Advances in carcinogenesis: a historical perspective from observational studies to tumor genome sequencing and TP53 mutation spectrum analysis. Biochim Biophys Acta 1816:199-208.
96. Soussi T. 2014. Locus-specific databases in cancer: what future in a post-genomic era? The TP53 LSDB paradigm. Hum Mutat 35:643-653.
97. Soussi T, Asselain B, Hamroun D, Kato S, Ishioka C, Claustres M, Beroud C. 2006a. Meta-analysis of the p53 mutation database for mutant p53 biological activity reveals a methodologic bias in mutation detection. Clin Cancer Res 12:62-69.
98. Soussi T, Beroud C. 2001. Assessing TP53 status in human tumours to evaluate clinical outcome. Nat Rev Cancer 1:233-240.
99. Soussi T, Beroud C. 2003. Significance of TP53 mutations in human cancer: a critical analysis of mutations at CpG dinucleotides. Hum Mutat 21:192-200.
100. Soussi T, Ishioka C, Claustres M, Beroud C. 2006b. Locus-specific mutation databases: pitfalls and good practice based on the p53 experience. Nat Rev Cancer 6:83-90.
101. Soussi T, Kato S, Levy PP, Ishioka C. 2005. Reassessment of the TP53 mutation database in human disease by data mining with a library of TP53 missense mutations. Hum Mutat 25:6-17.
102. Soussi T, Leroy B, Taschner PEM. 2014. Recommendations for analyzing and reporting TP53 gene alterations in the high throughput sequencing era. Hum Mutat 35:766-778.
103. Staib F, Hussain SP, Hofseth LJ, Wang XW, Harris CC. 2003. TP53 and liver carcinogenesis. Hum Mutat 21:201-216.
104. Stommel JM, Marchenko ND, Jimenez GS, Moll UM, Hope TJ, Wahl GM. 1999. A leucine-rich nuclear export signal in the p53 tetramerization domain: regulation of subcellular localization and p53 activity by NES masking. EMBO J 18:1660-1672.
105. Stratton MR. 2011. Exploring the genomes of cancer cells: progress and promise. Science 331:1553-1558.
106. Stratton MR, Campbell PJ, Futreal PA. 2009. The cancer genome. Nature 458:719-724.
107. Supek F, Minana B, Valcarcel J, Gabaldon T, Lehner B. 2014. Synonymous mutations frequently act as driver mutations in human cancers. Cell 156:1324-1335.
108. Takahashi T, Nau MM, Chiba I, Birrer MJ, Rosenberg RK, Vinocour M, Levitt M, Pass H, Gazdar AF, Minna JD. 1989. p53: a frequent target for genetic abnormalities in lung cancer. Science 246:491-494.
109. Terrier O, Bourdon JC, Rosa-Calatrava M. 2013. p53 protein isoforms: key regulators in the front line of pathogen infections? PLoS Pathog 9:e1003246.
110. Tornaletti S, Pfeifer GP. 1995. Complete and tissue-independent methylation of CpG sites in the p53 gene: implications for mutations in human cancers. Oncogene 10:1493-1499.
111. Toyooka S, Tsuda T, Gazdar AF. 2003. The TP53 gene, tobacco exposure, and lung cancer. Hum Mutat 21:229-239.
112. Valente LJ, Gray DH, Michalak EM, Pinon-Hofbauer J, Egle A, Scott CL, Janic A, Strasser A. 2013. p53 efficiently suppresses tumor development in the complete absence of its cell-cycle inhibitory and proapoptotic effectors p21, puma, and noxa. Cell Rep 3:1339-1345.
113. Varley JM, Chapman P, McGown G, Thorncroft M, White GR, Greaves MJ, Scott D, Spreadborough A, Tricker KJ, Birch JM, Evans DG, Reddel R, et al. 1998. Genetic and functional studies of a germline TP53 splicing mutation in a Li-Fraumeni-like family. Oncogene 16:3291-3298.
114. Vassilev LT. 2004. Small-molecule antagonists of p53-MDM2 binding: research tools and potential therapeutics. Cell Cycle 3:419-421.
115. Vousden KH, Lane DP. 2007. p53 in health and disease. Nat Rev Mol Cell Biol 8:275-283.
116. Wade M, Li YC, Wahl GM. 2013. MDM2, MDMX and p53 in oncogenesis and cancer therapy. Nat Rev Cancer 13:83-96.
117. Wang GS, Cooper TA. 2007. Splicing in disease: disruption of the splicing code and the decoding machinery. Nat Rev Genet 8:749-761.
118. Weigelt B, Geyer FC, Reis-Filho JS. 2010. Histological types of breast cancer: how special are they? Mol Oncol 4:192-208.
119. Wrighton KH. 2009. Small RNAs: p53 makes microRNAs mature. Nat Rev Cancer 9:612.
120. Xu-Monette ZY, Medeiros LJ, Li Y, Orlowski RZ, Andreeff M, Bueso-Ramos CE, Greiner TC, McDonnell TJ, Young KH. 2012. Dysfunction of the TP53 tumor suppressor gene in lymphoid malignancies. Blood 119:3668-3683.
121. You YH, Szabo PE, Pfeifer GP. 2000. Cyclobutane pyrimidine dimers form preferentially at the major p53 mutational hotspot in UVB-induced mouse skin tumors. Carcinogenesis 21:2113-2117.
122. Zhao CY, Grinkevich VV, Nikulenkov F, Bao W, Selivanova G. 2010. Rescue of the apoptotic-inducing function of mutant p53 by small molecule RITA. Cell Cycle 9:1847-1855.
123. Zheng R, Blobel GA. 2010. GATA transcription factors and cancer. Genes Cancer 1:1178-1188.
124. Zupnick A, Prives C. 2006. Mutational analysis of the p53 core domain L1 loop. J Biol Chem 281:20464-20473.