Genetic and epigenetic alterations as biomarkers for cancer detection, diagnosis and prognosis

Molecular Oncology

Volumn 1, Issue 1, 2007, Pages 26-41

  Herceg, Zdenko ^a   Hainaut, Pierre ^a  

^a INTERNATIONAL AGENCY FOR RESEARCH ON CANCER   (France)

Author keywords

Cancer biomarkers; Epigenetic changes; Genetic changes; Molecular signature; Prognosis

Indexed keywords

DNA METHYLTRANSFERASE; EPIDERMAL GROWTH FACTOR RECEPTOR; PROTEIN P16INK4A; PROTEIN P53; TUMOR MARKER;

CANCER; CANCER CELL; CANCER DIAGNOSIS; CANCER GENETICS; CANCER RISK; CARCINOGENESIS; CELL CLONING; CPG ISLAND; DNA METHYLATION; DNA REPLICATION; EPIGENETICS; GENE ACTIVATION; GENE EXPRESSION; GENE MUTATION; GENE SILENCING; GENETIC ANALYSIS; GENETIC STABILITY; HUMAN; ONCOGENE; PRIORITY JOURNAL; PROGNOSIS; REVIEW; TUMOR SUPPRESSOR GENE;

ANIMALS; EPIGENESIS, GENETIC; GENE EXPRESSION REGULATION, NEOPLASTIC; GENES, TUMOR SUPPRESSOR; HUMANS; NEOPLASM PROTEINS; NEOPLASMS; PROGNOSIS; TUMOR MARKERS, BIOLOGICAL;

EID: 34248678430     PISSN: 15747891     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.molonc.2007.01.004     Document Type: Review

References (152)

1. Abdel-Rahman W.M., Mecklin J.P., and Peltomaki P. The genetics of HNPCC: application to diagnosis and screening. Critical Reviews in Oncology-Hematology 58 (2006) 208-220
2. Abe M., Ohira M., Kaneda A., Yagi Y., Yamamoto S., Kitano Y., Takato T., Nakagawara A., and Ushijima T. CpG island methylator phenotype is a strong determinant of poor prognosis in neuroblastomas. Cancer Research 65 (2005) 828-834
3. Ahuja N., Mohan A.L., Li Q., Stolker J.M., Herman J.G., Hamilton S.R., Baylin S.B., and Issa J.P. Association between CpG island methylation and microsatellite instability in colorectal cancer. Cancer Research 57 (1997) 3370-3374
4. An Q., Liu Y., Gao Y., Huang J., Fong X., Li L., Zhang D., and Cheng S. Detection of p16 hypermethylation in circulating plasma DNA of non-small cell lung cancer patients. Cancer Letters 188 (2002) 109-114
5. An C., Choi I.S., Yao J.C., Worah S., Xie K., Mansfield P.F., Ajani J.A., Rashid A., Hamilton S.R., and Wu T.T. Prognostic significance of CpG island methylator phenotype and microsatellite instability in gastric carcinoma. Clinical Cancer Research 11 (2005) 656-663
6. Balko J.M., Potti A., Saunders C., Stromberg A., Haura E.B., and Black E.P. Gene expression patterns that predict sensitivity to epidermal growth factor receptor tyrosine kinase inhibitors in lung cancer cell lines and human lung tumors. BMC Genomics 7 (2006) 289
7. Bartel D.P. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116 (2004) 281-297
8. Bazan V., Bruno L., Augello C., Agnese V., Calo V., Corsale S., Gargano G., Terrasi M., Schiro V., Di Fede G., Adamo V., Intrivici C., Crosta A., Rinaldi G., Latteri F., Dardanoni G., Grassi N., Valerio M.R., Colucci G., Macaluso M., and Russo A. Molecular detection of TP53, Ki-Ras and p16INK4A promoter methylation in plasma of patients with colorectal cancer and its association with prognosis. Results of a 3-year GOIM (Gruppo Oncologico dell'Italia Meridionale) prospective study. Annals of Oncology 17 Suppl. 7 (2006) vii84-vii90
9. Bearzatto A., Conte D., Frattini M., Zaffaroni N., Andriani F., Balestra D., Tavecchio L., Daidone M.G., and Sozzi G. p16(INK4A) Hypermethylation detected by fluorescent methylation-specific PCR in plasmas from non-small cell lung cancer. Clinical Cancer Research 8 (2002) 3782-3787
10. Belinsky S.A. Gene-promoter hypermethylation as a biomarker in lung cancer. Nature Reviews Cancer 4 (2004) 707-717
11. Belinsky S.A., Nikula K.J., Palmisano W.A., Michels R., Saccomanno G., Gabrielson E., Baylin S.B., and Herman J.G. Aberrant methylation of p16(INK4a) is an early event in lung cancer and a potential biomarker for early diagnosis. Proceedings of the National Academy of Sciences of the United States of America 95 (1998) 11891-11896
12. Belinsky S.A., Palmisano W.A., Gilliland F.D., Crooks L.A., Divine K.K., Winters S.A., Grimes M.J., Harms H.J., Tellez C.S., Smith T.M., Moots P.P., Lechner J.F., Stidley C.A., and Crowell R.E. Aberrant promoter methylation in bronchial epithelium and sputum from current and former smokers. Cancer Research 62 (2002) 2370-2377
13. Belinsky S.A., Klinge D.M., Dekker J.D., Smith M.W., Bocklage T.J., Gilliland F.D., Crowell R.E., Karp D.D., Stidley C.A., and Picchi M.A. Gene promoter methylation in plasma and sputum increases with lung cancer risk. Clinical Cancer Research 11 (2005) 6505-6511
14. Bielas J.H., Loeb K.R., Rubin B.P., True L.D., and Loeb L.A. Human cancers express a mutator phenotype. Proceedings of the National Academy of Sciences of the United States of America 103 (2006) 18238-18242
15. Bird A. DNA methylation patterns and epigenetic memory. Genes and Development 16 (2002) 6-21
16. Cairns B.R. Emerging roles for chromatin remodeling in cancer biology. Trends in Cell Biology 11 (2001) S15-S21
17. Calin G.A., and Croce C.M. MicroRNA signatures in human cancers. Nature Reviews Cancer 6 (2006) 857-866
18. Cao R., Wang L., Wang H., Xia L., Erdjument-Bromage H., Tempst P., Jones R.S., and Zhang Y. Role of histone H3 lysine 27 methylation in polycomb-group silencing. Science 298 (2002) 1039-1043
19. Chan M.W., Chan L.W., Tang N.L., Tong J.H., Lo K.W., Lee T.L., Cheung H.Y., Wong W.S., Chan P.S., Lai F.M., and To K.F. Hypermethylation of multiple genes in tumor tissues and voided urine in urinary bladder cancer patients. Clinical Cancer Research 8 (2002) 464-470
20. Costello J.F., Fruhwald M.C., Smiraglia D.J., Rush L.J., Robertson G.P., Gao X., Wright F.A., Feramisco J.D., Peltomaki P., Lang J.C., Schuller D.E., Yu L., Bloomfield C.D., Caligiuri M.A., Yates A., Nishikawa R., Su Huang H., Petrelli N.J., Zhang X., O'Dorisio M.S., Held W.A., Cavenee W.K., and Plass C. Aberrant CpG-island methylation has non-random and tumour-type-specific patterns. Nature Genetics 24 (2000) 132-138
21. Cui H., Horon I.L., Ohlsson R., Hamilton S.R., and Feinberg A.P. Loss of imprinting in normal tissue of colorectal cancer patients with microsatellite instability. Nature Medicine 4 (1998) 1276-1280
22. Cui H., Cruz-Correa M., Giardiello F.M., Hutcheon D.F., Kafonek D.R., Brandenburg S., Wu Y., He X., Powe N.R., and Feinberg A.P. Loss of IGF2 imprinting: a potential marker of colorectal cancer risk. Science 299 (2003) 1753-1755
23. Dominguez G., Carballido J., Silva J., Silva J.M., Garcia J.M., Menendez J., Provencio M., Espana P., and Bonilla F. p14ARF promoter hypermethylation in plasma DNA as an indicator of disease recurrence in bladder cancer patients. Clinical Cancer Research 8 (2002) 980-985
24. Dulaimi E., Uzzo R.G., Greenberg R.E., Al-Saleem T., and Cairns P. Detection of bladder cancer in urine by a tumor suppressor gene hypermethylation panel. Clinical Cancer Research 10 (2004) 1887-1893
25. Eads C.A., Danenberg K.D., Kawakami K., Saltz L.B., Danenberg P.V., and Laird P.W. CpG island hypermethylation in human colorectal tumors is not associated with DNA methyltransferase overexpression. Cancer Research 59 (1999) 2302-2306
26. Eads C.A., Lord R.V., Wickramasinghe K., Long T.I., Kurumboor S.K., Bernstein L., Peters J.H., DeMeester S.R., DeMeester T.R., Skinner K.A., and Laird P.W. Epigenetic patterns in the progression of esophageal adenocarcinoma. Cancer Research 61 (2001) 3410-3418
27. Egger G., Liang G., Aparicio A., and Jones P.A. Epigenetics in human disease and prospects for epigenetic therapy. Nature 429 (2004) 457-463
28. Elenbaas B., Spirio L., Koerner F., Fleming M.D., Zimonjic D.B., Donaher J.L., Popescu N.C., Hahn W.C., and Weinberg R.A. Human breast cancer cells generated by oncogenic transformation of primary mammary epithelial cells. Genes and Development 15 (2001) 50-65
29. Esteller M., and Herman J.G. Generating mutations but providing chemosensitivity: the role of O6-methylguanine DNA methyltransferase in human cancer. Oncogene 23 (2004) 1-8
30. Esteller M., Levine R., Baylin S.B., Ellenson L.H., and Herman J.G. MLH1 promoter hypermethylation is associated with the microsatellite instability phenotype in sporadic endometrial carcinomas. Oncogene 17 (1998) 2413-2417
31. Esteller M., Sanchez-Cespedes M., Rosell R., Sidransky D., Baylin S.B., and Herman J.G. Detection of aberrant promoter hypermethylation of tumor suppressor genes in serum DNA from non-small cell lung cancer patients. Cancer Research 59 (1999) 67-70
32. Esteller M., Gaidano G., Goodman S.N., Zagonel V., Capello D., Botto B., Rossi D., Gloghini A., Vitolo U., Carbone A., Baylin S.B., and Herman J.G. Hypermethylation of the DNA repair gene O(6)-methylguanine DNA methyltransferase and survival of patients with diffuse large B-cell lymphoma. Journal of the National Cancer Institute 94 (2002) 26-32
33. Fackler M.J., Malone K., Zhang Z., Schilling E., Garrett-Mayer E., Swift-Scanlan T., Lange J., Nayar R., Davidson N.E., Khan S.A., and Sukumar S. Quantitative multiplex methylation-specific PCR analysis doubles detection of tumor cells in breast ductal fluid. Clinical Cancer Research 12 (2006) 3306-3310
34. Fearon E.R., and Vogelstein B. A genetic model for colorectal tumorigenesis. Cell 61 (1990) 759-767
35. Feinberg A.P., and Tycko B. The history of cancer epigenetics. Nature Reviews in Cancer 4 (2004) 143-153
36. Feinberg A.P., Ohlsson R., and Henikoff S. The epigenetic progenitor origin of human cancer. Nature Reviews 7 (2006) 21-33
37. Fishel R., and Wilson T. MutS homologs in mammalian cells. Current Opinion in Genetics and Development 7 (1997) 105-113
38. Forbes S., Clements J., Dawson E., Bamford S., Webb T., Dogan A., Flanagan A., Teague J., Wooster R., Futreal P.A., and Stratton M.R. Cosmic 2005. British Journal of Cancer 94 (2006) 318-322
39. Fraga M.F., Ballestar E., Villar-Garea A., Boix-Chornet M., Espada J., Schotta G., Bonaldi T., Haydon C., Ropero S., Petrie K., Iyer N.G., Perez-Rosado A., Calvo E., Lopez J.A., Cano A., Calasanz M.J., Colomer D., Piris M.A., Ahn N., Imhof A., Caldas C., Jenuwein T., and Esteller M. Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer. Nature Genetics 37 (2005) 391-400
40. Frolov M.V., and Dyson N.J. Molecular mechanisms of E2F-dependent activation and pRB-mediated repression. Journal of Cell Science 117 (2004) 2173-2181
41. Futreal P.A., Coin L., Marshall M., Down T., Hubbard T., Wooster R., Rahman N., and Stratton M.R. A census of human cancer genes. Nature Reviews in Cancer 4 (2004) 177-183
42. Garnis C., Buys T.P., and Lam W.L. Genetic alteration and gene expression modulation during cancer progression. Molecular Cancer 3 (2004) 9
43. Gayther S.A., Batley S.J., Linger L., Bannister A., Thorpe K., Chin S.F., Daigo Y., Russell P., Wilson A., Sowter H.M., Delhanty J.D., Ponder B.A., Kouzarides T., and Caldas C. Mutations truncating the EP300 acetylase in human cancers. Nature Genetics 24 (2000) 300-303
44. Gil J., and Peters G. Regulation of the INK4b-ARF-INK4a tumour suppressor locus: all for one or one for all. Nature Reviews in Molecular and Cellular Biology 7 (2006) 667-677
45. Goel A., Nagasaka T., Arnold C.N., Inoue T., Hamilton C., Niedzwiecki D., Compton C., Mayer R.J., Goldberg R., Bertagnolli M.M., and Boland C.R. The CpG Island Methylator Phenotype and Chromosomal Instability Are Inversely Correlated in Sporadic Colorectal Cancer. Gastroenterology (2006)
46. Goessl C., Sauter T., Michael T., Berge B., Staehler M., and Miller K. Efficacy and tolerability of tolterodine in children with detrusor hyperreflexia. Urology 55 (2000) 414-418
47. Goessl C., Muller M., Straub B., and Miller K. DNA alterations in body fluids as molecular tumor markers for urological malignancies. European Urology 41 (2002) 668-676
48. Gormally, E., Caboux, E., Vineis, P., Hainaut, P. Circulating free DNA in plasma or serum as biomarker of carcinogenesis: practical aspects and biological significance. Mutation Research, in press. (Epub ahead of print). doi:10.1016/j.mrrev.2006.11.002.
49. Gormally E., Vineis P., Matullo G., Veglia F., Caboux E., Le Roux E., Peluso M., Garte S., Guarrera S., Munnia A., Airoldi L., Autrup H., Malaveille C., Dunning A., Overvad K., Tjonneland A., Lund E., Clavel-Chapelon F., Boeing H., Trichopoulou A., Palli D., Krogh V., Tumino R., Panico S., Bueno-de-Mesquita H.B., Peeters P.H., Pera G., Martinez C., Dorronsoro M., Barricarte A., Navarro C., Quiros J.R., Hallmans G., Day N.E., Key T.J., Saracci R., Kaaks R., Riboli E., and Hainaut P. TP53 and KRAS2 mutations in plasma DNA of healthy subjects and subsequent cancer occurrence: a prospective study. Cancer Research 66 (2006) 6871-6876
50. Grady W.M., Rajput A., Lutterbaugh J.D., and Markowitz S.D. Detection of aberrantly methylated hMLH1 promoter DNA in the serum of patients with microsatellite unstable colon cancer. Cancer Research 61 (2001) 900-902
51. Guo M., Akiyama Y., House M.G., Hooker C.M., Heath E., Gabrielson E., Yang S.C., Han Y., Baylin S.B., Herman J.G., and Brock M.V. Hypermethylation of the GATA genes in lung cancer. Clinical Cancer Research 10 (2004) 7917-7924
52. Hainaut P., and Hollstein M. p53 and human cancer: the first ten thousand mutations. Advances in Cancer Research 77 (2000) 81-137
53. Hanahan D., and Weinberg R.A. The hallmarks of cancer. Cell 100 (2000) 57-70
54. Harari D., and Yarden Y. Molecular mechanisms underlying ErbB2/HER2 action in breast cancer. Oncogene 19 (2000) 6102-6114
55. Herman J.G., Umar A., Polyak K., Graff J.R., Ahuja N., Issa J.P., Markowitz S., Willson J.K., Hamilton S.R., Kinzler K.W., Kane M.F., Kolodner R.D., Vogelstein B., Kunkel T.A., and Baylin S.B. Incidence and functional consequences of hMLH1 promoter hypermethylation in colorectal carcinoma. Proceedings of the National Academy of Sciences of the United States of America 95 (1998) 6870-6875
56. Issa J.P. Methylation and prognosis: of molecular clocks and hypermethylator phenotypes. Clinical Cancer Research 9 (2003) 2879-2881
57. Issa J.P. CpG island methylator phenotype in cancer. Nature Reviews in Cancer 4 (2004) 988-993
58. Jackson P.E., Kuang S.Y., Wang J.B., Strickland P.T., Munoz A., Kensler T.W., Qian G.S., and Groopman J.D. Prospective detection of codon 249 mutations in plasma of hepatocellular carcinoma patients. Carcinogenesis 24 (2003) 1657-1663
59. Jaenisch R. DNA methylation and imprinting: why bother?. Trends in Genetics 13 (1997) 323-329
60. Jaenisch R., and Bird A. Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nature Genetics 33 Suppl. (2003) 245-254
61. Jenuwein T., and Allis C.D. Translating the histone code. Science 293 (2001) 1074-1080
62. Jeronimo C., Usadel H., Henrique R., Silva C., Oliveira J., Lopes C., and Sidransky D. Quantitative GSTP1 hypermethylation in bodily fluids of patients with prostate cancer. Urology 60 (2002) 1131-1135
63. John R.M., and Surani M.A. Genomic imprinting, mammalian evolution, and the mystery of egg-laying mammals. Cell 101 (2000) 585-588
64. Jones P.A., and Baylin S.B. The fundamental role of epigenetic events in cancer. Nature Reviews 3 (2002) 415-428
65. Kambara T., Simms L.A., Whitehall V.L., Spring K.J., Wynter C.V., Walsh M.D., Barker M.A., Arnold S., McGivern A., Matsubara N., Tanaka N., Higuchi T., Young J., Jass J.R., and Leggett B.A. BRAF mutation is associated with DNA methylation in serrated polyps and cancers of the colorectum. Gut 53 (2004) 1137-1144
66. Kane M.F., Loda M., Gaida G.M., Lipman J., Mishra R., Goldman H., Jessup J.M., and Kolodner R. Methylation of the hMLH1 promoter correlates with lack of expression of hMLH1 in sporadic colon tumors and mismatch repair-defective human tumor cell lines. Cancer Research 57 (1997) 808-811
67. Kaneda A., Kaminishi M., Yanagihara K., Sugimura T., and Ushijima T. Identification of silencing of nine genes in human gastric cancers. Cancer Research 62 (2002) 6645-6650
68. Kawakami K., Brabender J., Lord R.V., Groshen S., Greenwald B.D., Krasna M.J., Yin J., Fleisher A.S., Abraham J.M., Beer D.G., Sidransky D., Huss H.T., Demeester T.R., Eads C., Laird P.W., Ilson D.H., Kelsen D.P., Harpole D., Moore M.B., Danenberg K.D., Danenberg P.V., and Meltzer S.J. Hypermethylated APC DNA in plasma and prognosis of patients with esophageal adenocarcinoma. Journal of the National Cancer Institute 92 (2000) 1805-1811
69. Kim C.F., Jackson E.L., Woolfenden A.E., Lawrence S., Babar I., Vogel S., Crowley D., Bronson R.T., and Jacks T. Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell 121 (2005) 823-835
70. King C.M., Gillespie E.S., McKenna P.G., and Barnett Y.A. An investigation of mutation as a function of age in humans. Mutation Research 316 (1994) 79-90
71. Kurakawa E., Shimamoto T., Utsumi K., Hirano T., Kato H., and Ohyashiki K. Hypermethylation of p16(INK4a) and p15(INK4b) genes in non-small cell lung cancer. International Journal of Oncology 19 (2001) 277-281
72. Laird P.W. The power and the promise of DNA methylation markers. Nature Reviews in Cancer 3 (2003) 253-266
73. Lecomte T., Berger A., Zinzindohoue F., Micard S., Landi B., Blons H., Beaune P., Cugnenc P.H., and Laurent-Puig P. Detection of free-circulating tumor-associated DNA in plasma of colorectal cancer patients and its association with prognosis. International Journal of Cancer 100 (2002) 542-548
74. Lee T.L., Leung W.K., Chan M.W., Ng E.K., Tong J.H., Lo K.W., Chung S.C., Sung J.J., and To K.F. Detection of gene promoter hypermethylation in the tumor and serum of patients with gastric carcinoma. Clinical Cancer Research 8 (2002) 1761-1766
75. Liang G., Salem C.E., Yu M.C., Nguyen H.D., Gonzales F.A., Nguyen T.T., Nichols P.W., and Jones P.A. DNA methylation differences associated with tumor tissues identified by genome scanning analysis. Genomics 53 (1998) 260-268
76. Loizou J.I., Murr R., Finkbeiner M.G., Sawan C., Wang Z.Q., and Herceg Z. Epigenetic information in chromatin: the code of entry for DNA repair. Cell Cycle 5 (2006) 696-701
77. Lu J., Getz G., Miska E.A., Alvarez-Saavedra E., Lamb J., Peck D., Sweet-Cordero A., Ebert B.L., Mak R.H., Ferrando A.A., Downing J.R., Jacks T., Horvitz H.R., and Golub T.R. MicroRNA expression profiles classify human cancers. Nature 435 (2005) 834-838
78. Luedi P.P., Hartemink A.J., and Jirtle R.L. Genome-wide prediction of imprinted murine genes. Genome Research 15 (2005) 875-884
79. Marsit C.J., McClean M.D., Furniss C.S., and Kelsey K.T. Epigenetic inactivation of the SFRP genes is associated with drinking, smoking and HPV in head and neck squamous cell carcinoma. International Journal of Cancer 119 (2006) 1761-1766
80. Moulton T., Crenshaw T., Hao Y., Moosikasuwan J., Lin N., Dembitzer F., Hensle T., Weiss L., McMorrow L., Loew T., et al. Epigenetic lesions at the H19 locus in Wilms' tumour patients. Nature Genetics 7 (1994) 440-447
81. Muller H.M., Widschwendter A., Fiegl H., Ivarsson L., Goebel G., Perkmann E., Marth C., and Widschwendter M. DNA methylation in serum of breast cancer patients: an independent prognostic marker. Cancer Research 63 (2003) 7641-7645
82. Nakayama H., Hibi K., Taguchi M., Takase T., Yamazaki T., Kasai Y., Ito K., Akiyama S., and Nakao A. Molecular detection of p16 promoter methylation in the serum of colorectal cancer patients. Cancer Letters 188 (2002) 115-119
83. Nuovo G.J., Plaia T.W., Belinsky S.A., Baylin S.B., and Herman J.G. In situ detection of the hypermethylation-induced inactivation of the p16 gene as an early event in oncogenesis. Proceedings of the National Academy of Sciences of the United States of America 96 (1999) 12754-12759
84. Oakey R.J., and Beechey C.V. Imprinted genes: identification by chromosome rearrangements and post-genomic strategies. Trends in Genetics 18 (2002) 359-366
85. Olivier M., Eeles R., Hollstein M., Khan M.A., Harris C.C., and Hainaut P. The IARC TP53 database: new online mutation analysis and recommendations to users. Human Mutation 19 (2002) 607-614
86. Olivier M., Langerod A., Carrieri P., Bergh J., Klaar S., Eyfjord J., Theillet C., Rodriguez C., Lidereau R., Bieche I., Varley J., Bignon Y., Uhrhammer N., Winqvist R., Jukkola-Vuorinen A., Niederacher D., Kato S., Ishioka C., Hainaut P., and Borresen-Dale A.L. The clinical value of somatic TP53 gene mutations in 1,794 patients with breast cancer. Clinical Cancer Research 12 (2006) 1157-1167
87. Paez J.G., Janne P.A., Lee J.C., Tracy S., Greulich H., Gabriel S., Herman P., Kaye F.J., Lindeman N., Boggon T.J., Naoki K., Sasaki H., Fujii Y., Eck M.J., Sellers W.R., Johnson B.E., and Meyerson M. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 304 (2004) 1497-1500
88. Pao W., Miller V., Zakowski M., Doherty J., Politi K., Sarkaria I., Singh B., Heelan R., Rusch V., Fulton L., Mardis E., Kupfer D., Wilson R., Kris M., and Varmus H. EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib. Proceedings of the National Academy of Sciences of the United States of America 101 (2004) 13306-13311
89. Pao W., Miller V.A., Politi K.A., Riely G.J., Somwar R., Zakowski M.F., Kris M.G., and Varmus H. Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Medicine 2 (2005) e73
90. Papadopoulou E., Davilas E., Sotiriou V., Koliopanos A., Aggelakis F., Dardoufas K., Agnanti N.J., Karydas I., and Nasioulas G. Cell-free DNA and RNA in plasma as a new molecular marker for prostate cancer. Oncology Research 14 (2004) 439-445
91. Papadopoulou E., Davilas E., Sotiriou V., Georgakopoulos E., Georgakopoulou S., Koliopanos A., Aggelakis F., Dardoufas K., Agnanti N.J., Karydas I., and Nasioulas G. Cell-free DNA and RNA in plasma as a new molecular marker for prostate and breast cancer. Annals of the New York Academy of Sciences 1075 (2006) 235-243
92. Pardal R., Clarke M.F., and Morrison S.J. Applying the principles of stem-cell biology to cancer. Nature Reviews in Cancer 3 (2003) 895-902
93. Pasquinelli A.E., Hunter S., and Bracht J. MicroRNAs: a developing story. Current Opinion in Genetics and Development 15 (2005) 200-205
94. Peterson C.L., and Cote J. Cellular machineries for chromosomal DNA repair. Genes and Development 18 (2004) 602-616
95. Pray-Grant M.G., Daniel J.A., Schieltz D., Yates III J.R., and Grant P.A. Chd1 chromodomain links histone H3 methylation with SAGA- and SLIK-dependent acetylation. Nature 433 (2005) 434-438
96. Pulling L.C., Vuillemenot B.R., Hutt J.A., Devereux T.R., and Belinsky S.A. Aberrant promoter hypermethylation of the death-associated protein kinase gene is early and frequent in murine lung tumors induced by cigarette smoke and tobacco carcinogens. Cancer Research 64 (2004) 3844-3848
97. Ravenel J.D., Broman K.W., Perlman E.J., Niemitz E.L., Jayawardena T.M., Bell D.W., Haber D.A., Uejima H., and Feinberg A.P. Loss of imprinting of insulin-like growth factor-II (IGF2) gene in distinguishing specific biologic subtypes of Wilms tumor. Journal of the National Cancer Institute 93 (2001) 1698-1703
98. Roman-Gomez J., Jimenez-Velasco A., Agirre X., Prosper F., Heiniger A., and Torres A. Lack of CpG island methylator phenotype defines a clinical subtype of T-cell acute lymphoblastic leukemia associated with good prognosis. Journal of Clinical Oncology 23 (2005) 7043-7049
99. Rowley J.D. The critical role of chromosome translocations in human leukemias. Annual Review of Genetics 32 (1998) 495-519
100. Safar A.M., Spencer III H., Su X., Coffey M., Cooney C.A., Ratnasinghe L.D., Hutchins L.F., and Fan C.Y. Methylation profiling of archived non-small cell lung cancer: a promising prognostic system. Clinical Cancer Research 11 (2005) 4400-4405
101. Sakatani T., Kaneda A., Iacobuzio-Donahue C.A., Carter M.G., de Boom Witzel S., Okano H., Ko M.S., Ohlsson R., Longo D.L., and Feinberg A.P. Loss of imprinting of Igf2 alters intestinal maturation and tumorigenesis in mice. Science 307 (2005) 1976-1978
102. Samowitz W.S., Albertsen H., Herrick J., Levin T.R., Sweeney C., Murtaugh M.A., Wolff R.K., and Slattery M.L. Evaluation of a large, population-based sample supports a CpG island methylator phenotype in colon cancer. Gastroenterology 129 (2005) 837-845
103. Sanchez-Cespedes M., Esteller M., Wu L., Nawroz-Danish H., Yoo G.H., Koch W.M., Jen J., Herman J.G., and Sidransky D. Gene promoter hypermethylation in tumors and serum of head and neck cancer patients. Cancer research 60 (2000) 892-895
104. Santos-Rosa H., and Caldas C. Chromatin modifier enzymes, the histone code and cancer. European Journal of Cancer 41 (2005) 2381-2402
105. Schedin P., and Elias A. Multistep tumorigenesis and the microenvironment. Breast Cancer Research 6 (2004) 93-101
106. Schlesinger Y., Straussman R., Keshet I., Farkash S., Hecht M., Zimmerman J., Eden E., Yakhini Z., Ben-Shushan E., Reubinoff B.E., Bergman Y., Simon I., and Cedar H. Polycomb-mediated methylation on Lys27 of histone H3 pre-marks genes for de novo methylation in cancer. Nature Genetics (2006)
107. Schneider R., Bannister A.J., and Kouzarides T. Unsafe SETs: histone lysine methyltransferases and cancer. Trends in Biochemical Sciences 27 (2002) 396-402
108. Seligson D.B., Horvath S., Shi T., Yu H., Tze S., Grunstein M., and Kurdistani S.K. Global histone modification patterns predict risk of prostate cancer recurrence. Nature 435 (2005) 1262-1266
109. Sengupta S., Shimamoto A., Koshiji M., Pedeux R., Rusin M., Spillare E.A., Shen J.C., Huang L.E., Lindor N.M., Furuichi Y., and Harris C.C. Tumor suppressor p53 represses transcription of RECQ4 helicase. Oncogene 24 (2005) 1738-1748
110. Shaw R.J., Akufo-Tetteh E.K., Risk J.M., Field J.K., and Liloglou T. Methylation enrichment pyrosequencing: combining the specificity of MSP with validation by pyrosequencing. Nucleic Acids Research 34 (2006) e78
111. Shen L., Kondo Y., Hamilton S.R., Rashid A., and Issa J.P. P14 methylation in human colon cancer is associated with microsatellite instability and wild-type p53. Gastroenterology 124 (2003) 626-633
112. Sherr C.J., and Roberts J.M. CDK inhibitors: positive and negative regulators of G1-phase progression. Genes and Development 13 (1999) 1501-1512
113. Shibata D.M., Sato F., Mori Y., Perry K., Yin J., Wang S., Xu Y., Olaru A., Selaru F., Spring K., Young J., Abraham J.M., and Meltzer S.J. Hypermethylation of HPP1 is associated with hMLH1 hypermethylation in gastric adenocarcinomas. Cancer Research 62 (2002) 5637-5640
114. Shigematsu H., and Gazdar A.F. Somatic mutations of epidermal growth factor receptor signaling pathway in lung cancers. International Journal of Cancer 118 (2006) 257-262
115. Shigeno K., Yoshida H., Pan L., Luo J.M., Fujisawa S., Naito K., Nakamura S., Shinjo K., Takeshita A., Ohno R., and Ohnishi K. Disease-related potential of mutations in transcriptional cofactors CREB-binding protein and p300 in leukemias. Cancer Letters 213 (2004) 11-20
116. Singh S.K., Hawkins C., Clarke I.D., Squire J.A., Bayani J., Hide T., Henkelman R.M., Cusimano M.D., and Dirks P.B. Identification of human brain tumour initiating cells. Nature 432 (2004) 396-401
117. Sjoblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K., Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., and Velculescu V.E. The consensus coding sequences of human breast and colorectal cancers. Science 314 (2006) 268-274
118. Slattery M.L., Curtin K., Sweeney C., Levin T.R., Potter J., Wolff R.K., Albertsen H., and Samowitz W.S. Diet and lifestyle factor associations with CpG island methylator phenotype and BRAF mutations in colon cancer. International Journal of Cancer 120 (2007) 656-663
119. Sparmann A., and van Lohuizen M. Polycomb silencers control cell fate, development and cancer. Nature Reviews in Cancer 6 (2006) 846-856
120. Steenman M.J., Rainier S., Dobry C.J., Grundy P., Horon I.L., and Feinberg A.P. Loss of imprinting of IGF2 is linked to reduced expression and abnormal methylation of H19 in Wilms' tumour. Nature Genetics 7 (1994) 433-439
121. Strahl B.D., and Allis C.D. The language of covalent histone modifications. Nature 403 (2000) 41-45
122. Sugimura T., Terada M., Yokota J., Hirohashi S., and Wakabayashi K. Multiple genetic alterations in human carcinogenesis. Environmental Health Perspectives 98 (1992) 5-12
123. Surani M.A., Barton S.C., and Norris M.L. Development of reconstituted mouse eggs suggests imprinting of the genome during gametogenesis. Nature 308 (1984) 548-550
124. Taback B., Saha S., and Hoon D.S. Comparative analysis of mesenteric and peripheral blood circulating tumor DNA in colorectal cancer patients. Annals of the New York Academy of Sciences 1075 (2006) 197-203
125. Tada Y., Wada M., Taguchi K., Mochida Y., Kinugawa N., Tsuneyoshi M., Naito S., and Kuwano M. The association of death-associated protein kinase hypermethylation with early recurrence in superficial bladder cancers. Cancer Research 62 (2002) 4048-4053
126. Takano T., Ohe Y., Sakamoto H., Tsuta K., Matsuno Y., Tateishi U., Yamamoto S., Nokihara H., Yamamoto N., Sekine I., Kunitoh H., Shibata T., Sakiyama T., Yoshida T., and Tamura T. Epidermal growth factor receptor gene mutations and increased copy numbers predict gefitinib sensitivity in patients with recurrent non-small-cell lung cancer. Journal of Clinical Oncology 23 (2005) 6829-6837
127. Thibodeau S.N., French A.J., Roche P.C., Cunningham J.M., Tester D.J., Lindor N.M., Moslein G., Baker S.M., Liskay R.M., Burgart L.J., Honchel R., and Halling K.C. Altered expression of hMSH2 and hMLH1 in tumors with microsatellite instability and genetic alterations in mismatch repair genes. Cancer Research 56 (1996) 4836-4840
128. Toyooka S., Kiura K., and Mitsudomi T. EGFR mutation and response of lung cancer to gefitinib. The New England Journal of Medicine 352 (2005) 2136 (author reply 2136)
129. Toyota M., Ahuja N., Ohe-Toyota M., Herman J.G., Baylin S.B., and Issa J.P. CpG island methylator phenotype in colorectal cancer. Proceedings of the National Academy of Sciences of the United States of America 96 (1999) 8681-8686
130. Toyota M., Ohe-Toyota M., Ahuja N., and Issa J.P. Distinct genetic profiles in colorectal tumors with or without the CpG island methylator phenotype. Proceedings of the National Academy of Sciences of the United States of America 97 (2000) 710-715
131. Usadel H., Brabender J., Danenberg K.D., Jeronimo C., Harden S., Engles J., Danenberg P.V., Yang S., and Sidransky D. Quantitative adenomatous polyposis coli promoter methylation analysis in tumor tissue, serum, and plasma DNA of patients with lung cancer. Cancer Research 62 (2002) 371-375
132. Valenzuela M.T., Galisteo R., Zuluaga A., Villalobos M., Nunez M.I., Oliver F.J., and Ruiz de Almodovar J.M. Assessing the use of p16(INK4a) promoter gene methylation in serum for detection of bladder cancer. European Urology 42 (2002) 622-628 discussion 628-630
133. Varambally S., Dhanasekaran S.M., Zhou M., Barrette T.R., Kumar-Sinha C., Sanda M.G., Ghosh D., Pienta K.J., Sewalt R.G., Otte A.P., Rubin M.A., and Chinnaiyan A.M. The polycomb group protein EZH2 is involved in progression of prostate cancer. Nature 419 (2002) 624-629
134. Volinia S., Calin G.A., Liu C.G., Ambs S., Cimmino A., Petrocca F., Visone R., Iorio M., Roldo C., Ferracin M., Prueitt R.L., Yanaihara N., Lanza G., Scarpa A., Vecchione A., Negrini M., Harris C.C., and Croce C.M. A microRNA expression signature of human solid tumors defines cancer gene targets. Proceedings of the National Academy of Sciences of the United States of America 103 (2006) 2257-2261
135. Wang Y.C., Hsu H.S., Chen T.P., and Chen J.T. Molecular diagnostic markers for lung cancer in sputum and plasma. Annals of the New York Academy of Sciences 1075 (2006) 179-184
136. Ward R.L., Cheong K., Ku S.L., Meagher A., O'Connor T., and Hawkins N.J. Adverse prognostic effect of methylation in colorectal cancer is reversed by microsatellite instability. Journal of Clinical Oncology 21 (2003) 3729-3736
137. Weisenberger D.J., Siegmund K.D., Campan M., Young J., Long T.I., Faasse M.A., Kang G.H., Widschwendter M., Weener D., Buchanan D., Koh H., Simms L., Barker M., Leggett B., Levine J., Kim M., French A.J., Thibodeau S.N., Jass J., Haile R., and Laird P.W. CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer. Nature Genetics 38 (2006) 787-793
138. Widschwendter M., Fiegl H., Egle D., Mueller-Holzner E., Spizzo G., Marth C., Weisenberger D.J., Campan M., Young J., Jacobs I., and Laird P.W. Epigenetic stem cell signature in cancer. Nature Genetics (2006)
139. Wolffe A.P. Chromatin remodeling: why it is important in cancer. Oncogene 20 (2001) 2988-2990
140. Wong I.H., Lo Y.M., Zhang J., Liew C.T., Ng M.H., Wong N., Lai P.B., Lau W.Y., Hjelm N.M., and Johnson P.J. Detection of aberrant p16 methylation in the plasma and serum of liver cancer patients. Cancer Research 59 (1999) 71-73
141. Wong I.H., Lo Y.M., Yeo W., Lau W.Y., and Johnson P.J. Frequent p15 promoter methylation in tumor and peripheral blood from hepatocellular carcinoma patients. Clinical Cancer Research 6 (2000) 3516-3521
142. Wong T.S., Chang H.W., Tang K.C., Wei W.I., Kwong D.L., Sham J.S., Yuen A.P., and Kwong Y.L. High frequency of promoter hypermethylation of the death-associated protein-kinase gene in nasopharyngeal carcinoma and its detection in the peripheral blood of patients. Clinical Cancer Research 8 (2002) 433-437
143. Wong T.S., Man M.W., Lam A.K., Wei W.I., Kwong Y.L., and Yuen A.P. The study of p16 and p15 gene methylation in head and neck squamous cell carcinoma and their quantitative evaluation in plasma by real-time PCR. European Journal of Cancer 39 (2003) 1881-1887
144. Wong T.S., Kwong D.L., Sham J.S., Wei W.I., Kwong Y.L., and Yuen A.P. Quantitative plasma hypermethylated DNA markers of undifferentiated nasopharyngeal carcinoma. Clinical Cancer Research 10 (2004) 2401-2406
145. Woodson K., Flood A., Green L., Tangrea J.A., Hanson J., Cash B., Schatzkin A., and Schoenfeld P. Loss of insulin-like growth factor-II imprinting and the presence of screen-detected colorectal adenomas in women. Journal of the National Cancer Institute 96 (2004) 407-410
146. Yamamoto H., Min Y., Itoh F., Imsumran A., Horiuchi S., Yoshida M., Iku S., Fukushima H., and Imai K. Differential involvement of the hypermethylator phenotype in hereditary and sporadic colorectal cancers with high-frequency microsatellite instability. Genes, Chromosomes and Cancer 33 (2002) 322-325
147. Yan P.S., Perry M.R., Laux D.E., Asare A.L., Caldwell C.W., and Huang T.H. CpG island arrays: an application toward deciphering epigenetic signatures of breast cancer. Clinical Cancer Research 6 (2000) 1432-1438
148. Yang X.J. The diverse superfamily of lysine acetyltransferases and their roles in leukemia and other diseases. Nucleic acids research 32 (2004) 959-976
149. Zhang L., Huang J., Yang N., Greshock J., Megraw M.S., Giannakakis A., Liang S., Naylor T.L., Barchetti A., Ward M.R., Yao G., Medina A., O'Brien-Jenkins A., Katsaros D., Hatzigeorgiou A., Gimotty P.A., Weber B.L., and Coukos G. microRNAs exhibit high frequency genomic alterations in human cancer. Proceedings of the National Academy of Sciences of the United States of America 103 (2006) 9136-9141
150. Zhang Y.J., Rossner Jr. P., Chen Y., Agrawal M., Wang Q., Wang L., Ahsan H., Yu M.W., Lee P.H., and Santella R.M. Aflatoxin B1 and polycyclic aromatic hydrocarbon adducts, p53 mutations and p16 methylation in liver tissue and plasma of hepatocellular carcinoma patients. International Journal of Cancer 119 (2006) 985-991
151. Zhu P., Martin E., Mengwasser J., Schlag P., Janssen K.P., and Gottlicher M. Induction of HDAC2 expression upon loss of APC in colorectal tumorigenesis. Cancer Cell 5 (2004) 455-463
152. Zou H.Z., Yu B.M., Wang Z.W., Sun J.Y., Cang H., Gao F., Li D.H., Zhao R., Feng G.G., and Yi J. Detection of aberrant p16 methylation in the serum of colorectal cancer patients. Clinical Cancer Research 8 (2002) 188-191