DNA methylation-based biomarkers for early detection of non-small cell lung cancer: An update

Molecular Cancer

Volumn 7, Issue , 2008, Pages

  Anglim, Paul P ^a   Alonzo, Todd A ^b   Laird Offringa, Ite A ^a  

^a UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

^b UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BIOLOGICAL MARKER; MOLECULAR MARKER; TUMOR MARKER;

BLOOD ANALYSIS; BREATH ANALYSIS; DNA METHYLATION; EARLY DIAGNOSIS; HUMAN; LUNG LAVAGE; LUNG NON SMALL CELL CANCER; PROTEIN ANALYSIS; REVIEW; SENSITIVITY AND SPECIFICITY; SPUTUM ANALYSIS; SPUTUM CYTODIAGNOSIS; THORAX RADIOGRAPHY; CANCER DIAGNOSIS; METABOLISM;

CARCINOMA, NON-SMALL-CELL LUNG; DNA METHYLATION; EARLY DETECTION OF CANCER; HUMANS; TUMOR MARKERS, BIOLOGICAL;

EID: 56849133040     PISSN: None     EISSN: 14764598     Source Type: Journal    
DOI: 10.1186/1476-4598-7-81     Document Type: Review

References (168)

1. Molina JR Yang P Cassivi SD Schild SE Adjei AA Non-small cell lung cancer: Epidemiology, risk factors, treatment, and survivorship Mayo Clin Proc 2008, 83:584-594. 18452692
2. Jemal A Siegel R Ward E Murray T Xu J Thun MJ Cancer statistics, 2007 CA Cancer J Clin 2007, 57:43-66. 17237035
3. Henschke CI Yankelevitz DF Libby DM Pasmantier MW Smith JP Miettinen OS Survival of patients with stage I lung cancer detected on CT screening N Engl J Med 2006, 355:1763-1771. 10.1056/NEJMoa060476 17065637
4. Gavelli G Giampalma E Sensitivity and specificity of chest X-ray screening for lung cancer: Review article Cancer 2000, 89:2453-2456. 10.1002/1097-0142(20001201)89:11+<2453::AID-CNCR21>3.0.CO;2-M 11147625
5. Bach PB Kelley MJ Tate RC McCrory DC Screening for lung cancer: A review of the current literature Chest 2003, 123:72S-82S. 10.1378/ chest.123.1_suppl.72S 12527566
6. Diederich S Wormanns D Impact of low-dose CT on lung cancer screening Lung Cancer 2004, 45(Suppl 2):S13-19. 10.1016/j.lungcan.2004.07.997 15552777
7. Li R Todd NW Qiu Q Fan T Zhao RY Rodgers WH Fang HB Katz RL Stass SA Jiang F Genetic deletions in sputum as diagnostic markers for early detection of stage I non-small cell lung cancer Clin Cancer Res 2007, 13:482-487. 10.1158/1078-0432.CCR-06-1593 17255269
8. Lindell RM Hartman TE Swensen SJ Jett JR Midthun DE Tazelaar HD Mandrekar JN Five-year lung cancer screening experience: CT appearance, growth rate, location, and histologic features of 61 lung cancers Radiology 2007, 242:555-562. 10.1148/radiol.2422052090 17255425
9. Bastarrika G Garcia-Velloso MJ Lozano MD Montes U Torre W Spiteri N Campo A Seijo L Alcaide AB Pueyo J Cano D Vivas I Cosin O Dominguez P Serra P Richter JA Montuenga L Zulueta JJ Early lung cancer detection using spiral computed tomography and positron emission tomography Am J Respir Crit Care Med 2005, 171:1378-1383. 10.1164/rccm.200411-1479OC 15790860
10. Carter D Vazquez M Flieder DB Brambilla E Gazdar A Noguchi M Travis WD Kramer A Yip R Yankelevitz DF Henschke CI Comparison of pathologic findings of baseline and annual repeat cancers diagnosed on CT screening Lung Cancer 2007, 56:193-199. 10.1016/j.lungcan.2006.12.001 17239983
11. Gohagan J Marcus P Fagerstrom R Pinsky P Kramer B Prorok P Baseline findings of a randomized feasibility trial of lung cancer screening with spiral CT scan vs chest radiograph: The Lung Screening Study of the National Cancer Institute Chest 2004, 126:114-121. 10.1378/ chest.126.1.114 15249451
12. Gohagan JK Marcus PM Fagerstrom RM Pinsky PF Kramer BS Prorok PC Ascher S Bailey W Brewer B Church T Engelhard D Ford M Fouad M Freedman M Gelmann E Gierada D Hocking W Inampudi S Irons B Johnson CC Jones A Kucera G Kvale P Lappe K Manor W Moore A Nath H Neff S Oken M Plunkett M et al.: Final results of the Lung Screening Study, a randomized feasibility study of spiral CT versus chest X-ray screening for lung cancer Lung Cancer 2005, 47:9-15. 10.1016/j.lungcan.2004.06.007 15603850
13. Sone S Nakayama T Honda T Tsushima K Li F Haniuda M Takahashi Y Hanaoka T Takayama F Koizumi T Kubo K Yamanda T Kondo R Fushimi H Suzuki T CT findings of early-stage small cell lung cancer in a low-dose CT screening programme Lung Cancer 2007, 56:207-215. 10.1016/ j.lungcan.2006.12.014 17258349
14. van Klaveren RJ Habbema JDF Pedersen JH de Koning HJ Oudkerk M Hoogsteden HC Lung cancer screening by low-dose spiral computed tomography Eur Respir J 2001, 18:857-866. 10.1183/09031936.01.00076701 11757637
15. Jett JR Limitations of screening for lung cancer with low-dose spiral computed tomography Clin Cancer Res 2005, 11:4988s-4992s. 10.1158/ 1078-0432.CCR-05-9000 16000601
16. Crestanello JA Allen MS Jett JR Cassivi SD Nichols FC 3rd Swensen SJ Deschamps C Pairolero PC Thoracic surgical operations in patients enrolled in a computed tomographic screening trial J Thorac Cardiovasc Surg 2004, 128:254-259. 10.1016/j.jtcvs.2004.02.017 15282462
17. Yankelevitz DF Kostis WJ Henschke CI Heelan RT Libby DM Pasmantier MW Smith JP Overdiagnosis in chest radiographic screening for lung carcinoma: Frequency Cancer 2003, 97:1271-1275. 10.1002/cncr.11185 12599235
18. Hasegawa M Sone S Takashima S Li F Yang ZG Maruyama Y Watanabe T Growth rate of small lung cancers detected on mass CT screening Br J Radiol 2000, 73:1252-1259. 11205667
19. Bach PB Jett JR Pastorino U Tockman MS Swensen SJ Begg CB Computed tomography screening and lung cancer outcomes Jama 2007, 297:953-961. 10.1001/jama.297.9.953 17341709
20. Feller-Kopman D Lunn W Ernst A Autofluorescence bronchoscopy and endobronchial ultrasound: A practical review Ann Thorac Surg 2005, 80:2395-2401. 10.1016/j.athoracsur.2005.04.084 16305928
21. McWilliams A MacAulay C Gazdar AF Lam S Innovative molecular and imaging approaches for the detection of lung cancer and its precursor lesions Oncogene 2002, 21:6949-6959. 10.1038/sj.onc.1205831 12362276
22. Haussinger K Becker H Stanzel F Kreuzer A Schmidt B Strausz J Cavaliere S Herth F Kohlhaufl M Muller KM Huber RM Pichlmeier U Bolliger ChT Autofluorescence bronchoscopy with white light bronchoscopy compared with white light bronchoscopy alone for the detection of precancerous lesions: A European randomised controlled multicentre trial Thorax 2005, 60:496-503. 1747416 15923251 10.1136/thx.2005.041475
23. Weissleder R Pittet MJ Imaging in the era of molecular oncology Nature 2008, 452:580-589. 10.1038/nature06917 18385732
24. Rideout WM 3rd Eversole-Cire P Spruck CH 3rd Hustad CM Coetzee GA Gonzales FA Jones PA Progressive increases in the methylation status and heterochromatinization of the myoD CpG island during oncogenic transformation Mol Cell Biol 1994, 14:6143-6152. 359141 8065347
25. Takai D Jones PA The CpG island searcher: A new WWW resource In Silico Biol 2003, 3:235-240. 12954087
26. Suzuki MM Bird A DNA methylation landscapes: Provocative insights from epigenomics Nat Rev Genet 2008, 9:465-476. 10.1038/nrg2341 18463664
27. Tsou JA Galler JS Siegmund KD Laird PW Turla S Cozen W Hagen JA Koss MN Laird-Offringa IA Identification of a panel of sensitive and specific DNA methylation markers for lung adenocarcinoma Mol Cancer 2007, 6:70. 2206053 17967182 10.1186/1476-4598-6-70
28. Anglim PP Galler JS Koss MN Hagen JA Turla S Campan M Weisenberger DJ Laird PW Siegmund KD Laird-Offringa IA Identification of a panel of sensitive and specific DNA methylation markers for squamous cell lung cancer Mol Cancer 2008, 7:62. 2483990 18616821 10.1186/1476-4598-7-62
29. Belinsky SA Klinge DM Dekker JD Smith MW Bocklage TJ Gilliland FD Crowell RE Karp DD Stidley CA Picchi MA Gene promoter methylation in plasma and sputum increases with lung cancer risk Clin Cancer Res 2005, 11:6505-6511. 10.1158/1078-0432.CCR-05-0625 16166426
30. Kim H Kwon YM Kim JS Lee H Park JH Shim YM Han J Park J Kim DH Tumor-specific methylation in bronchial lavage for the early detection of non-small-cell lung cancer J Clin Oncol 2004, 22:2363-2370. 10.1200/ JCO.2004.10.077 15197197
31. Dai Z Popkie AP Zhu WG Timmers CD Raval A Tannehill-Gregg S Morrison CD Auer H Kratzke RA Niehans G Amatschek S Sommergruber W Leone GW Rosol T Otterson GA Plass C Bone morphogenetic protein 3B silencing in non-small-cell lung cancer Oncogene 2004, 23:3521-3529. 10.1038/ sj.onc.1207441 15116090
32. Marsit CJ Kim DH Liu M Hinds PW Wiencke JK Nelson HH Kelsey KT Hypermethylation of RASSF1A and BLU tumor suppressor genes in non-small cell lung cancer: Implications for tobacco smoking during adolescence Int J Cancer 2005, 114:219-223. 10.1002/ijc.20714 15540210
33. Toyooka KO Toyooka S Virmani AK Sathyanarayana UG Euhus DM Gilcrease M Minna JD Gazdar AF Loss of expression and aberrant methylation of the CDH13 (H-cadherin) gene in breast and lung carcinomas Cancer Res 2001, 61:4556-4560. 11389090
34. Toyooka S Toyooka KO Miyajima K Reddy JL Toyota M Sathyanarayana UG Padar A Tockman MS Lam S Shivapurkar N Gazdar AF Epigenetic down-regulation of death-associated protein kinase in lung cancers Clin Cancer Res 2003, 9:3034-3041. 12912953
35. Virmani AK Rathi A Sathyanarayana UG Padar A Huang CX Cunnigham HT Farinas AJ Milchgrub S Euhus DM Gilcrease M Herman J Minna JD Gazdar AF Aberrant methylation of the adenomatous polyposis coli (APC) gene promoter 1A in breast and lung carcinomas Clin Cancer Res 2001, 7:1998-2004. 11448917
36. Smith LT Lin M Brena RM Lang JC Schuller DE Otterson GA Morrison CD Smiraglia DJ Plass C Epigenetic regulation of the tumor suppressor gene TCF21 on 6q23-q24 in lung and head and neck cancer Proc Natl Acad Sci USA 2006, 103:982-987. 1348006 16415157 10.1073/pnas.0510171102
37. Tessema M Willink R Do K Yu YY Yu W Machida EO Brock M Van Neste L Stidley CA Baylin SB Belinsky SA Promoter methylation of genes in and around the candidate lung cancer susceptibility locus 6q23-25 Cancer Res 2008, 68:1707-1714. 10.1158/0008-5472.CAN-07-6325 18339850
38. Harden SV Tokumaru Y Westra WH Goodman S Ahrendt SA Yang SC Sidransky D Gene promoter hypermethylation in tumors and lymph nodes of stage I lung cancer patients Clin Cancer Res 2003, 9:1370-1375. 12684406
39. Topaloglu O Hoque MO Tokumaru Y Lee J Ratovitski E Sidransky D Moon CS Detection of promoter hypermethylation of multiple genes in the tumor and bronchoalveolar lavage of patients with lung cancer Clin Cancer Res 2004, 10:2284-2288. 10.1158/1078-0432.CCR-1111-3 15073103
40. Brabender J Usadel H Danenberg KD Metzger R Schneider PM Lord RV Wickramasinghe K Lum CE Park J Salonga D Singer J Sidransky D Holscher AH Meltzer SJ Danenberg PV Adenomatous polyposis coli gene promoter hypermethylation in non-small cell lung cancer is associated with survival Oncogene 2001, 20:3528-3532. 10.1038/sj.onc.1204455 11429699
41. Usadel H Brabender J Danenberg KD Jeronimo C Harden S Engles J Danenberg PV Yang S Sidransky D Quantitative adenomatous polyposis coli promoter methylation analysis in tumor tissue, serum, and plasma DNA of patients with lung cancer Cancer Res 2002, 62:371-375. 11809682
42. Nagatake M Osada H Kondo M Uchida K Nishio M Shimokata K Takahashi T Takahashi T Aberrant hypermethylation at the bcl-2 locus at 18q21 in human lung cancers Cancer Res 1996, 56:1886-1891. 8620509
43. Agathanggelou A Dallol A Zochbauer-Muller S Morrissey C Honorio S Hesson L Martinsson T Fong KM Kuo MJ Yuen PW Maher ER Minna JD Latif F Epigenetic inactivation of the candidate 3p21.3 suppressor gene BLU in human cancers Oncogene 2003, 22:1580-1588. 10.1038/sj.onc.1206243 12629521
44. Ito M Ito G Kondo M Uchiyama M Fukui T Mori S Yoshioka H Ueda Y Shimokata K Sekido Y Frequent inactivation of RASSF1A, BLU, and SEMA3B on 3p21.3 by promoter hypermethylation and allele loss in non-small cell lung cancer Cancer Lett 2005, 225:131-139. 10.1016/j.canlet.2004.10.041 15922865
45. Hsu HS Chen TP Hung CH Wen CK Lin RK Lee HC Wang YC Characterization of a multiple epigenetic marker panel for lung cancer detection and risk assessment in plasma Cancer 2007, 110:2019-2026. 10.1002/cncr.23001 17876837
46. Lee MN Tseng RC Hsu HS Chen JY Tzao C Ho WL Wang YC Epigenetic inactivation of the chromosomal stability control genes BRCA1, BRCA2, and XRCC5 in non-small cell lung cancer Clin Cancer Res 2007, 13:832-838. 10.1158/1078-0432.CCR-05-2694 17289874
47. Esteller M Corn PG Baylin SB Herman JG A gene hypermethylation profile of human cancer Cancer Res 2001, 61:3225-3229. 11309270
48. Zhong S Fields CR Su N Pan YX Robertson KD Pharmacologic inhibition of epigenetic modifications, coupled with gene expression profiling, reveals novel targets of aberrant DNA methylation and histone deacetylation in lung cancer Oncogene 2007, 26:2621-2634. 10.1038/ sj.onc.1210041 17043644
49. Nakata S Sugio K Uramoto H Oyama T Hanagiri T Morita M Yasumoto K The methylation status and protein expression of CDH1, p16(INK4A), and fragile histidine triad in nonsmall cell lung carcinoma: Epigenetic silencing, clinical features, and prognostic significance Cancer 2006, 106:2190-2199. 10.1002/cncr.21870 16598757
50. Kim JS Han J Shim YM Park J Kim DH Aberrant methylation of H-cadherin (CDH13) promoter is associated with tumor progression in primary nonsmall cell lung carcinoma Cancer 2005, 104:1825-1833. 10.1002/ cncr.21409 16177988
51. Sato M Mori Y Sakurada A Fujimura S Horii A The H-cadherin (CDH13) gene is inactivated in human lung cancer Hum Genet 1998, 103:96-101. 10.1007/ s004390050790 9737784
52. Ulivi P Zoli W Calistri D Fabbri F Tesei A Rosetti M Mengozzi M Amadori D p16INK4A and CDH13 hypermethylation in tumor and serum of non-small cell lung cancer patients J Cell Physiol 2006, 206:611-615. 10.1002/ jcp.20503 16222700
53. Jarmalaite S Kannio A Anttila S Lazutka JR Husgafvel-Pursiainen K Aberrant p16 promoter methylation in smokers and former smokers with nonsmall cell lung cancer Int J Cancer 2003, 106:913-918. 10.1002/ ijc.11322 12918069
54. Furonaka O Takeshima Y Awaya H Ishida H Kohno N Inai K Aberrant methylation of p14(ARF), p15(INK4b) and p16(INK4a) genes and location of the primary site in pulmonary squamous cell carcinoma Pathol Int 2004, 54:549-555. 10.1111/j.1440-1827.2004.01663.x 15260845
55. Liu Y An Q Li L Zhang D Huang J Feng X Cheng S Gao Y Hypermethylation of p16INK4a in Chinese lung cancer patients: Biological and clinical implications Carcinogenesis 2003, 24:1897-1901. 10.1093/carcin/bgg169 12970072
56. Liu Y Lan Q Siegfried JM Luketich JD Keohavong P Aberrant promoter methylation of p16 and MGMT genes in lung tumors from smoking and never-smoking lung cancer patients Neoplasia 2006, 8:46-51. 1584289 16533425 10.1593/neo.05586
57. Belinsky SA Nikula KJ Palmisano WA Michels R Saccomanno G Gabrielson E Baylin SB Herman JG Aberrant methylation of p16(INK4a) is an early event in lung cancer and a potential biomarker for early diagnosis Proc Natl Acad Sci USA 1998, 95:11891-11896. 21736 9751761 10.1073/pnas.95.20.11891
58. Breuer RH Snijders PJ Sutedja GT Sewalt RG Otte AP Postmus PE Meijer CJ Raaphorst FM Smit EF Expression of the p16(INK4a) gene product, methylation of the p16(INK4a) promoter region and expression of the polycomb-group gene BMI-1 in squamous cell lung carcinoma and premalignant endobronchial lesions Lung Cancer 2005, 48:299-306. 10.1016/ j.lungcan.2004.11.026 15892997
59. Cirincione R Lintas C Conte D Mariani L Roz L Vignola AM Pastorino U Sozzi G Methylation profile in tumor and sputum samples of lung cancer patients detected by spiral computed tomography: A nested case-control study Int J Cancer 2006, 118:1248-1253. 10.1002/ijc.21473 16152615
60. Fromont-Hankard G Philippe-Chomette P Delezoide AL Nessmann C Aigrain Y Peuchmaur M Glial cell-derived neurotrophic factor expression in normal human lung and congenital cystic adenomatoid malformation Arch Pathol Lab Med 2002, 126:432-436. 11900567
61. Mizuno K Osada H Konishi H Tatematsu Y Yatabe Y Mitsudomi T Fujii Y Takahashi T Aberrant hypermethylation of the CHFR prophase checkpoint gene in human lung cancers Oncogene 2002, 21:2328-2333. 10.1038/ sj.onc.1205402 11948416
62. Zhang P Wang J Gao W Yuan BZ Rogers J Reed E CHK2 kinase expression is down-regulated due to promoter methylation in non-small cell lung cancer Mol Cancer 2004, 3:14. 419366 15125777 10.1186/1476-4598-3-14
63. Yano M Toyooka S Tsukuda K Dote H Ouchida M Hanabata T Aoe M Date H Gazdar AF Shimizu N Aberrant promoter methylation of human DAB2 interactive protein (hDAB2IP) gene in lung cancers Int J Cancer 2005, 113:59-66. 10.1002/ijc.20531 15386433
64. Liu Y Gao W Siegfried JM Weissfeld JL Luketich JD Keohavong P Promoter methylation of RASSF1A and DAPK and mutations of K-ras, p53, and EGFR in lung tumors from smokers and never-smokers BMC Cancer 2007, 7:74. 1877812 17477876 10.1186/1471-2407-7-74
65. Luxen S Belinsky SA Knaus UG Silencing of DUOX NADPH oxidases by promoter hypermethylation in lung cancer Cancer Res 2008, 68:1037-1045. 10.1158/0008-5472.CAN-07-5782 18281478
66. Yue W Dacic S Sun Q Landreneau R Guo M Zhou W Siegfried JM Yu J Zhang L Frequent inactivation of RAMP2, EFEMP1 and Dutt1 in lung cancer by promoter hypermethylation Clin Cancer Res 2007, 13:4336-4344. 10.1158/ 1078-0432.CCR-07-0015 17671114
67. Tai KY Shiah SG Shieh YS Kao YR Chi CY Huang E Lee HS Chang LC Yang PC Wu CW DNA methylation and histone modification regulate silencing of epithelial cell adhesion molecule for tumor invasion and progression Oncogene 2007, 26:3989-3997. 10.1038/sj.onc.1210176 17213811
68. Chen H Suzuki M Nakamura Y Ohira M Ando S Iida T Nakajima T Nakagawara A Kimura H Aberrant methylation of FBN2 in human non-small cell lung cancer Lung Cancer 2005, 50:43-49. 10.1016/j.lungcan.2005.04.013 15951052
69. Tzao C Tsai HY Chen JT Chen CY Wang YC 5'CpG island hypermethylation and aberrant transcript splicing both contribute to the inactivation of the FHIT gene in resected non-small cell lung cancer Eur J Cancer 2004, 40:2175-2183. 10.1016/j.ejca.2004.06.022 15341994
70. Kim JS Kim H Shim YM Han J Park J Kim DH Aberrant methylation of the FHIT gene in chronic smokers with early stage squamous cell carcinoma of the lung Carcinogenesis 2004, 25:2165-2171. 10.1093/carcin/bgh217 15231689
71. Guo M Akiyama Y House MG Hooker CM Heath E Gabrielson E Yang SC Han Y Baylin SB Herman JG Brock MV Hypermethylation of the GATA genes in lung cancer Clin Cancer Res 2004, 10:7917-7924. 10.1158/1078-0432.CCR-04-1140 15585625
72. Irimia M Fraga MF Sanchez-Cespedes M Esteller M CpG island promoter hypermethylation of the Ras-effector gene NORE1A occurs in the context of a wild-type K-ras in lung cancer Oncogene 2004, 23:8695-8699. 10.1038/ sj.onc.1207914 15378027
73. Shigematsu H Suzuki M Takahashi T Miyajima K Toyooka S Shivapurkar N Tomlinson GE Mastrangelo D Pass HI Brambilla E Sathyanarayana UG Czerniak B Fujisawa T Shimizu N Gazdar AF Aberrant methylation of HIN-1 (high in normal-1) is a frequent event in many human malignancies Int J Cancer 2005, 113:600-604. 10.1002/ijc.20622 15472908
74. Takai D Yagi Y Wakazono K Ohishi N Morita Y Sugimura T Ushijima T Silencing of HTR1B and reduced expression of EDN1 in human lung cancers, revealed by methylation-sensitive representational difference analysis Oncogene 2001, 20:7505-7513. 10.1038/sj.onc.1204940 11709722
75. Dunn JR Panutsopulos D Shaw MW Heighway J Dormer R Salmo EN Watson SG Field JK Liloglou T METH-2 silencing and promoter hypermethylation in NSCLC Br J Cancer 2004, 91:1149-1154. 15328519
76. Sathyanarayana UG Toyooka S Padar A Takahashi T Brambilla E Minna JD Gazdar AF Epigenetic inactivation of laminin-5-encoding genes in lung cancers Clin Cancer Res 2003, 9:2665-2672. 12855645
77. Wang YC Lu YP Tseng RC Lin RK Chang JW Chen JT Shih CM Chen CY Inactivation of hMLH1 and hMSH2 by promoter methylation in primary non-small cell lung tumors and matched sputum samples J Clin Invest 2003, 111:887-895. 153761 12639995
78. Nishioka M Kohno T Tani M Yanaihara N Tomizawa Y Otsuka A Sasaki S Kobayashi K Niki T Maeshima A Sekido Y Minna JD Sone S Yokota J MYO18B, a candidate tumor suppressor gene at chromosome 22q12.1, deleted, mutated, and methylated in human lung cancer Proc Natl Acad Sci USA 2002, 99:12269-12274. 129434 12209013 10.1073/pnas.192445899
79. Brena RM Morrison C Liyanarachchi S Jarjoura D Davuluri RV Otterson GA Reisman D Glaros S Rush LJ Plass C Aberrant DNA methylation of OLIG1, a novel prognostic factor in non-small cell lung cancer PLoS Med 2007, 4:e108. 1831740 17388669 10.1371/journal.pmed.0040108
80. Palmisano WA Crume KP Grimes MJ Winters SA Toyota M Esteller M Joste N Baylin SB Belinsky SA Aberrant promoter methylation of the transcription factor genes PAX5 alpha and beta in human cancers Cancer Res 2003, 63:4620-4625. 12907641
81. Gery S Komatsu N Kawamata N Miller CW Desmond J Virk RK Marchevsky A McKenna R Taguchi H Koeffler HP Epigenetic silencing of the candidate tumor suppressor gene Per1 in non-small cell lung cancer Clin Cancer Res 2007, 13:1399-1404. 10.1158/1078-0432.CCR-06-1730 17332281
82. Xu L Jain RK Down-regulation of placenta growth factor by promoter hypermethylation in human lung and colon carcinoma Mol Cancer Res 2007, 5:873-880. 10.1158/1541-7786.MCR-06-0141 17704140
83. Cooper WN Dickinson RE Dallol A Grigorieva EV Pavlova TV Hesson LB Bieche I Broggini M Maher ER Zabarovsky ER Clark GJ Latif F Epigenetic regulation of the ras effector/tumour suppressor RASSF2 in breast and lung cancer Oncogene 2008, 27:1805-1811. 10.1038/sj.onc.1210805 17891178
84. Kaira K Sunaga N Tomizawa Y Yanagitani N Ishizuka T Saito R Nakajima T Mori M Epigenetic inactivation of the RAS-effector gene RASSF2 in lung cancers Int J Oncol 2007, 31:169-173. 17549418
85. Choi N Son DS Song I Lee HS Lim YS Song MS Lim DS Lee J Kim H Kim J RASSF1A is not appropriate as an early detection marker or a prognostic marker for non-small cell lung cancer Int J Cancer 2005, 115:575-581. 10.1002/ijc.20916 15700308
86. Wang J Walsh G Liu DD Lee JJ Mao L Expression of Delta DNMT3B variants and its association with promoter methylation of p16 and RASSF1A in primary non-small cell lung cancer Cancer Res 2006, 66:8361-8366. 10.1158/0008-5472.CAN-06-2031 16951144
87. Burbee DG Forgacs E Zochbauer-Muller S Shivakumar L Fong K Gao B Randle D Kondo M Virmani A Bader S Sekido Y Latif F Milchgrub S Toyooka S Gazdar AF Lerman MI Zabarovsky E White M Minna JD Epigenetic inactivation of RASSF1A in lung and breast cancers and malignant phenotype suppression J Natl Cancer Inst 2001, 93:691-699. 10.1093/jnci/ 93.9.691 11333291
88. Chang HC Cho CY Hung WC Downregulation of RECK by promoter methylation correlates with lymph node metastasis in non-small cell lung cancer Cancer Sci 2007, 98:169-173. 10.1111/j.1349-7006.2006.00367.x 17233834
89. Li QL Kim HR Kim WJ Choi JK Lee YH Kim HM Li LS Kim H Chang J Ito Y Youl Lee K Bae SC Transcriptional silencing of the RUNX3 gene by CpG hypermethylation is associated with lung cancer Biochem Biophys Res Commun 2004, 314:223-228. 10.1016/j.bbrc.2003.12.079 14715269
90. He B You L Uematsu K Zang K Xu Z Lee AY Costello JF McCormick F Jablons DM SOCS-3 is frequently silenced by hypermethylation and suppresses cell growth in human lung cancer Proc Natl Acad Sci USA 2003, 100:14133-14138. 283558 14617776 10.1073/pnas.2232790100
91. Suzuki M Shigematsu H Nakajima T Kubo R Motohashi S Sekine Y Shibuya K Iizasa T Hiroshima K Nakatani Y Gazdar AF Fujisawa T Synchronous alterations of Wnt and epidermal growth factor receptor signaling pathways through aberrant methylation and mutation in non small cell lung cancer Clin Cancer Res 2007, 13:6087-6092. 10.1158/ 1078-0432.CCR-07-0591 17947472
92. Fukui T Kondo M Ito G Maeda O Sato N Yoshioka H Yokoi K Ueda Y Shimokata K Sekido Y Transcriptional silencing of secreted frizzled related protein 1 (SFRP 1) by promoter hypermethylation in non-small-cell lung cancer Oncogene 2005, 24:6323-6327. 10.1038/sj.onc.1208777 16007200
93. Xu XL Wu LC Du F Davis A Peyton M Tomizawa Y Maitra A Tomlinson G Gazdar AF Weissman BE Bowcock AM Baer R Minna JD Inactivation of human SRBC, located within the 11p15.5-p15.4 tumor suppressor region, in breast and lung cancers Cancer Res 2001, 61:7943-7949. 11691816
94. Kuramochi M Fukuhara H Nobukuni T Kanbe T Maruyama T Ghosh HP Pletcher M Isomura M Onizuka M Kitamura T Sekiya T Reeves RH Murakami Y TSLC1 is a tumor-suppressor gene in human non-small-cell lung cancer Nat Genet 2001, 27:427-430. 10.1038/86934 11279526
95. Fukami T Fukuhara H Kuramochi M Maruyama T Isogai K Sakamoto M Takamoto S Murakami Y Promoter methylation of the TSLC1 gene in advanced lung tumors and various cancer cell lines Int J Cancer 2003, 107:53-59. 10.1002/ijc.11348 12925956
96. Kikuchi S Yamada D Fukami T Maruyama T Ito A Asamura H Matsuno Y Onizuka M Murakami Y Hypermethylation of the TSLC1/IGSF4 promoter is associated with tobacco smoking and a poor prognosis in primary nonsmall cell lung carcinoma Cancer 2006, 106:1751-1758. 10.1002/cncr.21800 16534787
97. Shivapurkar N Stastny V Xie Y Prinsen C Frenkel E Czerniak B Thunnissen FB Minna JD Gazdar AF Differential methylation of a short CpG-rich sequence within exon 1 of TCF21 gene: A promising cancer biomarker assay Cancer Epidemiol Biomarkers Prev 2008, 17:995-1000. 10.1158/ 1055-9965.EPI-07-2808 18398044
98. Wang G Hu X Lu C Su C Luo S Luo ZW Promoter-hypermethylation associated defective expression of E-cadherin in primary non-small cell lung cancer Lung Cancer 2008.
99. Chan EC Lam SY Tsang KW Lam B Ho JC Fu KH Lam WK Kwong YL Aberrant promoter methylation in Chinese patients with non-small cell lung cancer: Patterns in primary tumors and potential diagnostic application in bronchoalevolar lavage Clin Cancer Res 2002, 8:3741-3746. 12473584
100. Guo M House MG Hooker C Han Y Heath E Gabrielson E Yang SC Baylin SB Herman JG Brock MV Promoter hypermethylation of resected bronchial margins: A field defect of changes? Clin Cancer Res 2004, 10:5131-5136. 10.1158/1078-0432.CCR-03-0763 15297416
101. Shivapurkar N Toyooka S Toyooka KO Reddy J Miyajima K Suzuki M Shigematsu H Takahashi T Parikh G Pass HI Chaudhary PM Gazdar AF Aberrant methylation of trail decoy receptor genes is frequent in multiple tumor types Int J Cancer 2004, 109:786-792. 10.1002/ijc.20041 14999791
102. Brabender J Usadel H Metzger R Schneider PM Park J Salonga D Tsao-Wei DD Groshen S Lord RV Takebe N Schneider S Holscher AH Danenberg KD Danenberg PV Quantitative O(6)-methylguanine DNA methyltransferase methylation analysis in curatively resected non-small cell lung cancer: associations with clinical outcome Clin Cancer Res 2003, 9:223-227. 12538473
103. Furonaka O Takeshima Y Awaya H Kushitani K Kohno N Inai K Aberrant methylation and loss of expression of O-methylguanine-DNA methyltransferase in pulmonary squamous cell carcinoma and adenocarcinoma Pathol Int 2005, 55:303-309. 10.1111/ j.1440-1827.2005.01830.x 15943786
104. Fong KM Sekido Y Gazdar AF Minna JD Lung cancer. 9: Molecular biology of lung cancer: Clinical implications Thorax 2003, 58:892-900. 1746489 14514947 10.1136/thorax.58.10.892
105. Suzuki M Shigematsu H Iizasa T Hiroshima K Nakatani Y Minna JD Gazdar AF Fujisawa T Exclusive mutation in epidermal growth factor receptor gene, HER-2, and KRAS, and synchronous methylation of nonsmall cell lung cancer Cancer 2006, 106:2200-2207. 10.1002/cncr.21853 16598760
106. Tang M Torres-Lanzas J Lopez-Rios F Esteller M Sanchez-Cespedes M Wnt signaling promoter hypermethylation distinguishes lung primary adenocarcinomas from colorectal metastasis to the lung Int J Cancer 2006, 119:2603-2606. 10.1002/ijc.22211 16991125
107. Tsou JA Shen LY Siegmund KD Long TI Laird PW Seneviratne CK Koss MN Pass HI Hagen JA Laird-Offringa IA Distinct DNA methylation profiles in malignant mesothelioma, lung adenocarcinoma, and non-tumor lung Lung Cancer 2005, 47:193-204. 10.1016/j.lungcan.2004.08.003 15639718
108. Wang Y Zhang D Zheng W Luo J Bai Y Lu Z Multiple gene methylation of nonsmall cell lung cancers evaluated with 3-dimensional microarray Cancer 2008, 112:1325-1336. 10.1002/cncr.23312 18286531
109. Kim DS Cha SI Lee JH Lee YM Choi JE Kim MJ Lim JS Lee EB Kim CH Park TI Jung TH Park JY Aberrant DNA methylation profiles of non-small cell lung cancers in a Korean population Lung Cancer 2007, 58:1-6. 10.1016/ j.lungcan.2007.04.008 17532092
110. Yanagawa N Tamura G Oizumi H Takahashi N Shimazaki Y Motoyama T Promoter hypermethylation of tumor suppressor and tumor-related genes in non-small cell lung cancers Cancer Sci 2003, 94:589-592. 10.1111/ j.1349-7006.2003.tb01487.x 12841866
111. Sano A Kage H Sugimoto K Kitagawa H Aki N Goto A Fukayama M Nakajima J Takamoto S Nagase T Yatomi Y Ohishi N Takai D A second-generation profiling system for quantitative methylation analysis of multiple gene promoters: Application to lung cancer Oncogene 2007, 26:6518-6525. 10.1038/sj.onc.1210483 17452971
112. Zochbauer-Muller S Fong KM Virmani AK Geradts J Gazdar AF Minna JD Aberrant promoter methylation of multiple genes in non-small cell lung cancers Cancer Res 2001, 61:249-255. 11196170
113. Shivapurkar N Stastny V Suzuki M Wistuba II Li L Zheng Y Feng Z Hol B Prinsen C Thunnissen FB Gazdar AF Application of a methylation gene panel by quantitative PCR for lung cancers Cancer Lett 2007, 247:56-71. 10.1016/j.canlet.2006.03.020 16644104
114. Safar AM Spencer H 3rd Su X Coffey M Cooney CA Ratnasinghe LD Hutchins LF Fan CY Methylation profiling of archived non-small cell lung cancer: a promising prognostic system Clin Cancer Res 2005, 11:4400-4405. 10.1158/1078-0432.CCR-04-2378 15958624
115. Marsit CJ Houseman EA Christensen BC Eddy K Bueno R Sugarbaker DJ Nelson HH Karagas MR Kelsey KT Examination of a CpG island methylator phenotype and implications of methylation profiles in solid tumors Cancer Res 2006, 66:10621-10629. 10.1158/0008-5472.CAN-06-1687 17079487
116. Dammann R Strunnikova M Schagdarsurengin U Rastetter M Papritz M Hattenhorst UE Hofmann HS Silber RE Burdach S Hansen G CpG island methylation and expression of tumour-associated genes in lung carcinoma Eur J Cancer 2005, 41:1223-1236. 10.1016/j.ejca.2005.02.020 15911247
117. Feng Q Hawes SE Stern JE Wiens L Lu H Dong ZM Jordan CD Kiviat NB Vesselle H DNA methylation in tumor and matched normal tissues from non-small cell lung cancer patients Cancer Epidemiol Biomarkers Prev 2008, 17:645-654. 10.1158/1055-9965.EPI-07-2518 18349282
118. Ehrich M Field JK Liloglou T Xinarianos G Oeth P Nelson MR Cantor CR Boom van den D Cytosine methylation profiles as a molecular marker in non-small cell lung cancer Cancer Res 2006, 66:10911-10918. 10.1158/ 0008-5472.CAN-06-0400 17108128
119. Field JK Liloglou T Warrak S Burger M Becker E Berlin K Nimmrich I Maier S Methylation discriminators in NSCLC identified by a microarray based approach Int J Oncol 2005, 27:105-111. 15942649
120. Fukasawa M Kimura M Morita S Matsubara K Yamanaka S Endo C Sakurada A Sato M Kondo T Horii A Sasaki H Hatada I Microarray analysis of promoter methylation in lung cancers J Hum Genet 2006, 51:368-374. 10.1007/ s10038-005-0355-4 16435073
121. Dai Z Lakshmanan RR Zhu WG Smiraglia DJ Rush LJ Fruhwald MC Brena RM Li B Wright FA Ross P Otterson GA Plass C Global methylation profiling of lung cancer identifies novel methylated genes Neoplasia 2001, 3:314-323. 1505864 11571631 10.1038/sj.neo.7900162
122. Bibikova M Lin Z Zhou L Chudin E Garcia EW Wu B Doucet D Thomas NJ Wang Y Vollmer E Goldmann T Seifart C Jiang W Barker DL Chee MS Floros J Fan JB High-throughput DNA methylation profiling using universal bead arrays Genome Res 2006, 16:383-393. 1415217 16449502 10.1101/gr.4410706
123. Hatada I Fukasawa M Kimura M Morita S Yamada K Yoshikawa T Yamanaka S Endo C Sakurada A Sato M Kondo T Horii A Ushijima T Sasaki H Genome-wide profiling of promoter methylation in human Oncogene 2006, 25:3059-3064. 10.1038/sj.onc.1209331 16407832
124. Shames DS Girard L Gao B Sato M Lewis CM Shivapurkar N Jiang A Perou CM Kim YH Pollack JR Fong KM Lam CL Wong M Shyr Y Nanda R Olopade OI Gerald W Euhus DM Shay JW Gazdar AF Minna JD A genome-wide screen for promoter methylation in lung cancer identifies novel methylation markers for multiple malignancies PLoS Med 2006, 3:e486. 1716188 17194187 10.1371/ journal.pmed.0030486
125. Cortese R Hartmann O Berlin K Eckhardt F Correlative gene expression and DNA methylation profiling in lung development nominate new biomarkers in lung cancer Int J Biochem Cell Biol 2008, 40:1494-1508. 10.1016/ j.biocel.2007.11.018 18203646
126. Rauch T Li H Wu X Pfeifer GP MIRA-assisted microarray analysis, a new technology for the determination of DNA methylation patterns, identifies frequent methylation of homeodomain-containing genes in lung cancer cells Cancer Res 2006, 66:7939-7947. 10.1158/0008-5472.CAN-06-1888 16912168
127. Rauch TA Zhong X Wu X Wang M Kernstine KH Wang Z Riggs AD Pfeifer GP High-resolution mapping of DNA hypermethylation and hypomethylation in lung cancer Proc Natl Acad Sci USA 2008, 105:252-257. 2224196 18162535 10.1073/pnas.0710735105
128. Rauch T Wang Z Zhang X Zhong X Wu X Lau SK Kernstine KH Riggs AD Pfeifer GP Homeobox gene methylation in lung cancer studied by genome-wide analysis with a microarray-based methylated CpG island recovery assay Proc Natl Acad Sci USA 2007, 104:5527-5532. 1838508 17369352 10.1073/ pnas.0701059104
129. Widschwendter M Fiegl H Egle D Mueller-Holzner E Spizzo G Marth C Weisenberger DJ Campan M Young J Jacobs I Laird PW Epigenetic stem cell signature in cancer Nat Genet 2007, 39:157-158. 10.1038/ng1941 17200673
130. Zhou W Heist RS Liu G Neuberg DS Asomaning K Su L Wain JC Lynch TJ Giovannucci E Christiani DC Polymorphisms of vitamin D receptor and survival in early-stage non-small cell lung cancer patients Cancer Epidemiol Biomarkers Prev 2006, 15:2239-2245. 10.1158/ 1055-9965.EPI-06-0023 17119052
131. Vischioni B Oudejans JJ Vos W Rodriguez JA Giaccone G Frequent overexpression of aurora B kinase, a novel drug target, in non-small cell lung carcinoma patients Mol Cancer Ther 2006, 5:2905-2913. 10.1158/ 1535-7163.MCT-06-0301 17121938
132. Tam IY Chung LP Suen WS Wang E Wong MC Ho KK Lam WK Chiu SW Girard L Minna JD Gazdar AF Wong MP Distinct epidermal growth factor receptor and KRAS mutation patterns in non-small cell lung cancer patients with different tobacco exposure and clinicopathologic features Clin Cancer Res 2006, 12:1647-1653. 10.1158/1078-0432.CCR-05-1981 16533793
133. Raponi M Zhang Y Yu J Chen G Lee G Taylor JM Macdonald J Thomas D Moskaluk C Wang Y Beer DG Gene expression signatures for predicting prognosis of squamous cell and adenocarcinomas of the lung Cancer Res 2006, 66:7466-7472. 10.1158/0008-5472.CAN-06-1191 16885343
134. Shapiro B Chakrabarty M Cohn EM Leon SA Determination of circulating DNA levels in patients with benign or malignant gastrointestinal disease Cancer 1983, 51:2116-2120 10.1002/ 1097-0142(19830601)51:11<2116::AID-CNCR2820511127>3.0.CO;2-S 6188527
135. Hagiwara N Mechanic LE Trivers GE Cawley HL Taga M Bowman ED Kumamoto K He P Bernard M Doja S Miyashita M Tajiri T Sasajima K Nomura T Makino H Takahashi K Hussain SP Harris CC Quantitative detection of p53 mutations in plasma DNA from tobacco smokers Cancer Res 2006, 66:8309-8317. 10.1158/0008-5472.CAN-06-0991 16912213
136. Sozzi G Musso K Ratcliffe C Goldstraw P Pierotti MA Pastorino U Detection of microsatellite alterations in plasma DNA of non-small cell lung cancer patients: A prospect for early diagnosis Clin Cancer Res 1999, 5:2689-2692. 10537330
137. Khan S Coulson JM Woll PJ Genetic abnormalities in plasma DNA of patients with lung cancer and other respiratory diseases Int J Cancer 2004, 110:891-895. 10.1002/ijc.20156 15170672
138. Laird PW Jaenisch R The role of DNA methylation in cancer genetic and epigenetics Annu Rev Genet 1996, 30:441-464. 10.1146/ annurev.genet.30.1.441 8982461
139. Widschwendter M Menon U Circulating methylated DNA: A new generation of tumor markers Clin Cancer Res 2006, 12:7205-7208. 10.1158/ 1078-0432.CCR-06-2531 17189390
140. Belinsky SA Grimes MJ Casas E Stidley CA Franklin WA Bocklage TJ Johnson DH Schiller JH Predicting gene promoter methylation in non-small-cell lung cancer by evaluating sputum and serum Br J Cancer 2007, 96:1278-1283. 10.1038/sj.bjc.6603721 17406356
141. Di Vinci A Gelvi I Banelli B Casciano I Allemanni G Romani M Meth-DOP-PCR: An assay for the methylation profiling of trace amounts of DNA extracted from bodily fluids Lab Invest 2006, 86:297-303. 10.1038/ labinvest.3700384 16446707
142. Esteller M Sanchez-Cespedes M Rosell R Sidransky D Baylin SB Herman JG Detection of aberrant promoter hypermethylation of tumor suppressor genes in serum DNA from non-small cell lung cancer patients Cancer Res 1999, 59:67-70. 9892187
143. Fujiwara K Fujimoto N Tabata M Nishii K Matsuo K Hotta K Kozuki T Aoe M Kiura K Ueoka H Tanimoto M Identification of epigenetic aberrant promoter methylation in serum DNA is useful for early detection of lung cancer Clin Cancer Res 2005, 11:1219-1225. 10.1158/1078-0432.CCR-04-2363 15709192
144. Wang Y Yu Z Wang T Zhang J Hong L Chen L Identification of epigenetic aberrant promoter methylation of RASSF1A in serum DNA and its clinicopathological significance in lung cancer Lung Cancer 2007, 56:289-294. 10.1016/j.lungcan.2006.12.007 17267069
145. Virmani AK Tsou JA Siegmund KD Shen LY Long TI Laird PW Gazdar AF Laird-Offringa IA Hierarchical clustering of lung cancer cell lines using DNA methylation markers Cancer Epidemiol Biomarkers Prev 2002, 11:291-297. 11895880
146. Miozzo M Sozzi G Musso K Pilotti S Incarbone M Pastorino U Pierotti MA Microsatellite alterations in bronchial and sputum specimens of lung cancer patients Cancer Res 1996, 56:2285-2288. 8625300
147. Belinsky SA Liechty KC Gentry FD Wolf HJ Rogers J Vu K Haney J Kennedy TC Hirsch FR Miller Y Franklin WA Herman JG Baylin SB Bunn PA Byers T Promoter hypermethylation of multiple genes in sputum precedes lung cancer incidence in a high-risk cohort Cancer Res 2006, 66:3338-3344. 10.1158/0008-5472.CAN-05-3408 16540689
148. Olaussen KA Soria JC Park YW Kim HJ Kim SH Ro JY Andre F Jang SJ Assessing abnormal gene promoter methylation in paraffin-embedded sputum from patients with NSCLC Eur J Cancer 2005, 41:2112-2119. 10.1016/ j.ejca.2005.06.013 16129599
149. Palmisano WA Divine KK Saccomanno G Gilliland FD Baylin SB Herman JG Belinsky SA Predicting lung cancer by detecting aberrant promoter methylation in sputum Cancer Res 2000, 60:5954-5958. 11085511
150. Hunt J Exhaled breath condensate: An evolving tool for noninvasive evaluation of lung disease J Allergy Clin Immunol 2002, 110:28-34. 10.1067/mai.2002.124966 12110814
151. Carpagnano GE Foschino-Barbaro MP Resta O Gramiccioni E Carpagnano F Endothelin-1 is increased in the breath condensate of patients with non-small-cell lung cancer Oncology 2004, 66:180-184. 10.1159/000077992 15218307
152. Carpagnano GE Resta O Foschino-Barbaro MP Gramiccioni E Carpagnano F Interleukin-6 is increased in breath condensate of patients with non-small cell lung cancer Int J Biol Markers 2002, 17:141-145. 12113582
153. Carpagnano GE Foschino-Barbaro MP Mule G Resta O Tommasi S Mangia A Carpagnano F Stea G Susca A Di Gioia G De Lena M Paradiso A 3p microsatellite alterations in exhaled breath condensate from patients with non-small cell lung cancer Am J Respir Crit Care Med 2005, 172:738-744. 10.1164/rccm.200503-439OC 15947287
154. Gessner C Kuhn H Toepfer K Hammerschmidt S Schauer J Wirtz H Detection of p53 gene mutations in exhaled breath condensate of non-small cell lung cancer patients Lung Cancer 2004, 43:215-222. 10.1016/ j.lungcan.2003.08.034 14739043
155. Ahrendt SA Chow JT Xu LH Yang SC Eisenberger CF Esteller M Herman JG Wu L Decker PA Jen J Sidransky D Molecular detection of tumor cells in bronchoalveolar lavage fluid from patients with early stage lung cancer J Natl Cancer Inst 1999, 91:332-339. 10.1093/jnci/91.4.332 10050866
156. Grote HJ Schmiemann V Kiel S Bocking A Kappes R Gabbert HE Sarbia M Aberrant methylation of the adenomatous polyposis coli promoter 1A in bronchial aspirates from patients with suspected lung cancer Int J Cancer 2004, 110:751-755. 10.1002/ijc.20196 15146565
157. de Fraipont F Moro-Sibilot D Michelland S Brambilla E Brambilla C Favrot MC Promoter methylation of genes in bronchial lavages: A marker for early diagnosis of primary and relapsing non-small cell lung cancer? Lung Cancer 2005, 50:199-209. 10.1016/j.lungcan.2005.05.019 16043258
158. Grote HJ Schmiemann V Geddert H Bocking A Kappes R Gabbert HE Sarbia M Methylation of RAS association domain family protein 1A as a biomarker of lung cancer Cancer 2006, 108:129-134. 10.1002/cncr.21717 16444703
159. Grote HJ Schmiemann V Geddert H Rohr UP Kappes R Gabbert HE Bocking A Aberrant promoter methylation of p16(INK4a), RARB2 and SEMA3B in bronchial aspirates from patients with suspected lung cancer Int J Cancer 2005, 116:720-725. 10.1002/ijc.21090 15849750
160. Schmiemann V Bocking A Kazimirek M Onofre AS Gabbert HE Kappes R Gerharz CD Grote HJ Methylation assay for the diagnosis of lung cancer on bronchial aspirates: A cohort study Clin Cancer Res 2005, 11:7728-7734. 10.1158/1078-0432.CCR-05-0999 16278393
161. Kramer B Gohagan J Prorok P Cancer Screening: Theory and Practice Marcel Dekker 1999.
162. Cancer of the Lung and Bronchus http://seer.cancer.gov/statfacts/html/ lungb.html
163. Bain C Feskanich D Speizer FE Thun M Hertzmark E Rosner BA Colditz GA Lung cancer rates in men and women with comparable histories of smoking J Natl Cancer Inst 2004, 96:826-834. 15173266
164. Bearzatto A Conte D Frattini M Zaffaroni N Andriani F Balestra D Tavecchio L Daidone MG Sozzi G p16(INK4A) Hypermethylation detected by fluorescent methylation-specific PCR in plasmas from non-small cell lung cancer Clin Cancer Res 2002, 8:3782-3787. 12473590
165. Xie GS Hou AR Li LY Gao YN Cheng SJ Aberrant p16 promoter hypermethylation in bronchial mucosae as a biomarker for the early detection of lung cancer Chin Med J (Engl) 2006, 119:1469-1472. 16989749
166. Pepe MS Etzioni R Feng Z Potter JD Thompson ML Thornquist M Winget M Yasui Y Phases of biomarker development for early detection of cancer J Natl Cancer Inst 2001, 93:1054-1061. 10.1093/jnci/93.14.1054 11459866
167. American Cancer Society http://www.cancer.org
168. Sun S Schiller JH Gazdar AF Lung cancer in never smokers-a different disease Nat Rev Cancer 2007, 7:778-790. 10.1038/nrc2190 17882278