© 2000 by Oxford University Press
Journal of the National Cancer Institute, Vol. 92, No. 22, 1805-1811,
November 15, 2000
© 2000 Oxford University Press
Hypermethylated APC DNA in Plasma and Prognosis of Patients With Esophageal Adenocarcinoma
Affiliations of authors: K. Kawakami, J. Brabender, K. D. Danenberg, P. V. Danenberg (Department of Biochemistry and Molecular Biology and Norris Cancer Center), R. V. Lord, T. R. Demeester (Department of Surgery), S. Groshen (Department of Biostatistics and Epidemiology), Keck School of Medicine, University of Southern California, Los Angeles; B. D. Greenwald, J. Yin, A. S. Fleisher, J. M. Abraham, S. J. Meltzer (Department of Medicine, Gastroenterology Division), M. J. Krasna (Division of Thoracic Surgery and Surgical Oncology), Greenebaum Cancer Center, University of Maryland School of Medicine, and Baltimore Veterans Affairs Hospital; D. G. Beer, Department of Surgery, University of Michigan School of Medicine, Ann Arbor; D. Sidransky, Division of Head and Neck Cancer Research, The Johns Hopkins University, Baltimore; H. T. Huss, D. H. Ilson, D. P. Kelsen, Gastroenterology Oncology Service, Memorial Sloan-Kettering Cancer Center, Cornell University Medical College, New York, NY; C. Eads, P. W. Laird, Department of Biochemistry and Molecular Biology and Norris Cancer Center and Department of Surgery, University of Southern California Keck School of Medicine; D. Harpole, M. Moore, Department of Surgery, Duke University Medical Center, Durham, NC.
Correspondence to: Stephen J. Meltzer, M.D., University of Maryland School of Medicine, 22 S. Greene St., Rm. N3W62, Baltimore, MD 21201 (e-mail: smeltzer{at}medicine.umaryland.edu).
Background: The adenomatous polyposis coli (APC) locus on chromosome 5q21–22 shows frequent loss of heterozygosity (LOH) in esophageal carcinomas. However, the prevalence of truncating mutations in the APC gene in esophageal carcinomas is low. Because hypermethylation of promoter regions is known to affect several other tumor suppressor genes, we investigated whether the APC promoter region is hypermethylated in esophageal cancer patients and whether this abnormality could serve as a prognostic plasma biomarker. Methods: We assayed DNA from tumor tissue and matched plasma from esophageal cancer patients for hypermethylation of the promoter region of the APC gene. We used the maximal chi-square statistic to identify a discriminatory cutoff value for hypermethylated APC DNA levels in plasma and used bootstrap-like simulations to determine the P value to test for the strength of this association. This cutoff value was used to generate Kaplan–Meier survival curves. All P values were based on two-sided tests. Results: Hypermethylation of the promoter region of the APC gene occurred in abnormal esophageal tissue in 48 (92%) of 52 patients with esophageal adenocarcinoma, in 16 (50%) of 32 patients with esophageal squamous cell carcinoma, and in 17 (39.5%) of 43 patients with Barrett's metaplasia but not in matching normal esophageal tissues. Hypermethylated APC DNA was observed in the plasma of 13 (25%) of 52 adenocarcinoma patients and in two (6.3%) of 32 squamous carcinoma patients. High plasma levels of methylated APC DNA were statistically significantly associated with reduced patient survival (P = .016). Conclusion: The APC promoter region was hypermethylated in tumors of the majority of patients with primary esophageal adenocarcinomas. Levels of hypermethylated APC gene DNA in the plasma may be a useful biomarker of biologically aggressive disease in esophageal adenocarcinoma patients and should be evaluated as a potential biomarker in additional tumor types.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. S. Kim, K. Yamashita, Y. K. Chae, Y. Tokumaru, X. Chang, M. Zahurak, M. Osada, H. L. Park, A. Chuang, J. A. Califano, et al. A Promoter Methylation Pattern in the N-Methyl-D-Aspartate Receptor 2B Gene Predicts Poor Prognosis in Esophageal Squamous Cell Carcinoma Clin. Cancer Res., November 15, 2007; 13(22): 6658 - 6665. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Jin, A. Olaru, J. Yang, F. Sato, Y. Cheng, T. Kan, Y. Mori, C. Mantzur, B. Paun, J. P. Hamilton, et al. Hypermethylation of Tachykinin-1 Is a Potential Biomarker in Human Esophageal Cancer Clin. Cancer Res., November 1, 2007; 13(21): 6293 - 6300. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Zagorowicz and J. Jankowski Molecular changes in the progression of Barrett's oesophagus Postgrad. Med. J., August 1, 2007; 83(982): 529 - 535. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Righini, F. de Fraipont, J.-F. Timsit, C. Faure, E. Brambilla, E. Reyt, and M.-C. Favrot Tumor-Specific Methylation in Saliva: A Promising Biomarker for Early Detection of Head and Neck Cancer Recurrence Clin. Cancer Res., February 15, 2007; 13(4): 1179 - 1185. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Lagarde, F. J. W. ten Kate, D. J. Richel, G. J. A. Offerhaus, and J. J. B. van Lanschot Molecular Prognostic Factors in Adenocarcinoma of the Esophagus and Gastroesophageal Junction Ann. Surg. Oncol., February 1, 2007; 14(2): 977 - 991. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Widschwendter and U. Menon Circulating Methylated DNA: A New Generation of Tumor Markers Clin. Cancer Res., December 15, 2006; 12(24): 7205 - 7208. [Full Text] [PDF]
|
|
|
|
 |
|
 L Murray, A Sedo, M Scott, D McManus, J M Sloan, L J Hardie, D Forman, and C P Wild TP53 and progression from Barrett's metaplasia to oesophageal adenocarcinoma in a UK population cohort Gut, October 1, 2006; 55(10): 1390 - 1397. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. O. Hoque, Q. Feng, P. Toure, A. Dem, C. W. Critchlow, S. E. Hawes, T. Wood, C. Jeronimo, E. Rosenbaum, J. Stern, et al. Detection of Aberrant Methylation of Four Genes in Plasma DNA for the Detection of Breast Cancer J. Clin. Oncol., September 10, 2006; 24(26): 4262 - 4269. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. L. Wang, T.-T. Wu, E. Resetkova, H. Wang, A. M. Correa, W. L. Hofstetter, S. G. Swisher, J. A. Ajani, A. Rashid, S. R. Hamilton, et al. Expression of Annexin A1 in Esophageal and Esophagogastric Junction Adenocarcinomas: Association with Poor Outcome Clin. Cancer Res., August 1, 2006; 12(15): 4598 - 4604. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Kim, K. Yamashita, J. H. Baek, H. L. Park, A. L. Carvalho, M. Osada, M. O. Hoque, S. Upadhyay, M. Mori, C. Moon, et al. N-methyl-D-aspartate receptor type 2B is epigenetically inactivated and exhibits tumor-suppressive activity in human esophageal cancer. Cancer Res., April 1, 2006; 66(7): 3409 - 3418. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Yamashita, H. L. Park, M. S. Kim, M. Osada, Y. Tokumaru, H. Inoue, M. Mori, and D. Sidransky PGP9.5 Methylation in Diffuse-Type Gastric Cancer. Cancer Res., April 1, 2006; 66(7): 3921 - 3927. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. R. DeMeester Adenocarcinoma of the Esophagus and Cardia: A Review of the Disease and Its Treatment Ann. Surg. Oncol., January 1, 2006; 13(1): 12 - 30. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. F. Souza and S. J. Spechler Concepts in the Prevention of Adenocarcinoma of the Distal Esophagus and Proximal Stomach CA Cancer J Clin, November 1, 2005; 55(6): 334 - 351. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. V. Brock, C. M. Hooker, R. Yung, M. Guo, Y. Han, S. E. Ames, D. Chang, S. C. Yang, D. Mason, M. Sussman, et al. Can We Improve the Cytologic Examination of Malignant Pleural Effusions Using Molecular Analysis? Ann. Thorac. Surg., October 1, 2005; 80(4): 1241 - 1247. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. O. Hoque, O. Topaloglu, S. Begum, R. Henrique, E. Rosenbaum, W. Van Criekinge, W. H. Westra, and D. Sidransky Quantitative Methylation-Specific Polymerase Chain Reaction Gene Patterns in Urine Sediment Distinguish Prostate Cancer Patients From Control Subjects J. Clin. Oncol., September 20, 2005; 23(27): 6569 - 6575. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Miyamoto and T. Ushijima Diagnostic and Therapeutic Applications of Epigenetics Jpn. J. Clin. Oncol., June 1, 2005; 35(6): 293 - 301. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. L. Mandelker, K. Yamashita, Y. Tokumaru, K. Mimori, D. L. Howard, Y. Tanaka, A. L. Carvalho, W.-W. Jiang, H. L. Park, M. S. Kim, et al. PGP9.5 Promoter Methylation Is an Independent Prognostic Factor for Esophageal Squamous Cell Carcinoma Cancer Res., June 1, 2005; 65(11): 4963 - 4968. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L.-C. Li, P. R. Carroll, and R. Dahiya Epigenetic Changes in Prostate Cancer: Implication for Diagnosis and Treatment J Natl Cancer Inst, January 19, 2005; 97(2): 103 - 115. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. J. Herrera, S. Raja, W. E. Gooding, T. El-Hefnawy, L. Kelly, J. D. Luketich, and T. E. Godfrey Quantitative Analysis of Circulating Plasma DNA as a Tumor Marker in Thoracic Malignancies Clin. Chem., January 1, 2005; 51(1): 113 - 118. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M. Das and R. Singal DNA Methylation and Cancer J. Clin. Oncol., November 15, 2004; 22(22): 4632 - 4642. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. K. Leung, K.-F. To, E. P.S. Man, M. W.Y. Chan, A. H.C. Bai, A. J. Hui, F. K.L. Chan, J. F.Y. Lee, and J. J. Y. Sung Detection of Epigenetic Changes in Fecal DNA as a Molecular Screening Test for Colorectal Cancer: A Feasibility Study Clin. Chem., November 1, 2004; 50(11): 2179 - 2182. [Full Text] [PDF]
|
|
|
|
|
|
G. Clement, F. T. Bosman, C. Fontolliet, and J. Benhattar Monoallelic Methylation of the APC Promoter Is Altered in Normal Gastric Mucosa Associated with Neoplastic Lesions Cancer Res., October 1, 2004; 64(19): 6867 - 6873. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A M Gilbey, D Burnett, R E Coleman, and I Holen The detection of circulating breast cancer cells in blood J. Clin. Pathol., September 1, 2004; 57(9): 903 - 911. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Mori, J. Yin, F. Sato, A. Sterian, L. A. Simms, F. M. Selaru, K. Schulmann, Y. Xu, A. Olaru, S. Wang, et al. Identification of Genes Uniquely Involved in Frequent Microsatellite Instability Colon Carcinogenesis by Expression Profiling Combined with Epigenetic Scanning Cancer Res., April 1, 2004; 64(7): 2434 - 2438. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. T. McManus, A. Olaru, and S. J. Meltzer Biomarkers of Esophageal Adenocarcinoma and Barrett's Esophagus Cancer Res., March 1, 2004; 64(5): 1561 - 1569. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. von Knobloch, H. Brandt, A. J. Schrader, A. Heidenreich, and R. Hofmann Molecular Serological Detection of DNA Alterations in Transitional Cell Carcinoma Is Highly Sensitive and Stage Independent Clin. Cancer Res., February 1, 2004; 10(3): 988 - 993. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Widschwendter, H. M. Muller, H. Fiegl, L. Ivarsson, A. Wiedemair, E. Muller-Holzner, G. Goebel, C. Marth, and M. Widschwendter DNA Methylation in Serum and Tumors of Cervical Cancer Patients Clin. Cancer Res., January 15, 2004; 10(2): 565 - 571. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Kopelovich, J. A. Crowell, and J. R. Fay The Epigenome as a Target for Cancer Chemoprevention J Natl Cancer Inst, December 3, 2003; 95(23): 1747 - 1757. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. M. Muller, A. Widschwendter, H. Fiegl, L. Ivarsson, G. Goebel, E. Perkmann, C. Marth, and M. Widschwendter DNA Methylation in Serum of Breast Cancer Patients: An Independent Prognostic Marker Cancer Res., November 15, 2003; 63(22): 7641 - 7645. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. V. Brock, M. Gou, Y. Akiyama, A. Muller, T.-T. Wu, E. Montgomery, M. Deasel, P. Germonpre, L. Rubinson, R. F. Heitmiller, et al. Prognostic Importance of Promoter Hypermethylation of Multiple Genes in Esophageal Adenocarcinoma Clin. Cancer Res., August 1, 2003; 9(8): 2912 - 2919. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Matsubayashi, N. Sato, N. Fukushima, C. J. Yeo, K. M. Walter, K. Brune, F. Sahin, R. H. Hruban, and M. Goggins Methylation of Cyclin D2 Is Observed Frequently in Pancreatic Cancer but Is Also an Age-related Phenomenon in Gastrointestinal Tissues Clin. Cancer Res., April 1, 2003; 9(4): 1446 - 1452. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Brabender, H. Usadel, R. Metzger, P. M. Schneider, J. Park, D. Salonga, D. D. Tsao-Wei, S. Groshen, R. V. Lord, N. Takebe, et al. Quantitative O6-Methylguanine DNA Methyltransferase Methylation Analysis in Curatively Resected Non-Small Cell Lung Cancer: Associations with Clinical Outcome Clin. Cancer Res., January 1, 2003; 9(1): 223 - 227. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Silva, J. Silva, A. Sanchez, J. M. Garcia, G. Dominguez, M. Provencio, L. Sanfrutos, E. Jareno, A. Colas, P. Espana, et al. Tumor DNA in Plasma at Diagnosis of Breast Cancer Patients Is a Valuable Predictor of Disease-free Survival Clin. Cancer Res., December 1, 2002; 8(12): 3761 - 3766. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Lee, W. H. Kim, H.-Y. Jung, M. H. Yang, and G. H. Kang Aberrant CpG Island Methylation of Multiple Genes in Intrahepatic Cholangiocarcinoma Am. J. Pathol., September 1, 2002; 161(3): 1015 - 1022. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. Johnson and Y.M. D. Lo Plasma Nucleic Acids in the Diagnosis and Management of Malignant Disease Clin. Chem., August 1, 2002; 48(8): 1186 - 1193. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. I. Auvinen, E. I.T. Sihvo, T. Ruohtula, J. T. Salminen, A. Koivistoinen, P. Siivola, R. Ronnholm, J. O. Ramo, M. Bergman, and J. A. Salo Incipient Angiogenesis in Barrett's Epithelium and Lymphangiogenesis in Barrett's Adenocarcinoma J. Clin. Oncol., July 1, 2002; 20(13): 2971 - 2979. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. K. C. Ngan, T. T. C. Yip, W.-W. Cheng, J. K. C. Chan, W. C. S. Cho, V. W. S. Ma, K.-K. Wan, S.-K. Au, C.-K. Law, and W.-H. Lau Circulating Epstein-Barr Virus DNA in Serum of Patients with Lymphoepithelioma-like Carcinoma of the Lung: A Potential Surrogate Marker for Monitoring Disease Clin. Cancer Res., April 1, 2002; 8(4): 986 - 994. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Lehmann, F. Langer, H. Feist, S. Glockner, B. Hasemeier, and H. Kreipe Quantitative Assessment of Promoter Hypermethylation during Breast Cancer Development Am. J. Pathol., February 1, 2002; 160(2): 605 - 612. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Usadel, J. Brabender, K. D. Danenberg, C. Jeronimo, S. Harden, J. Engles, P. V. Danenberg, S. Yang, and D. Sidransky Quantitative Adenomatous Polyposis Coli Promoter Methylation Analysis in Tumor Tissue, Serum, and Plasma DNA of Patients with Lung Cancer Cancer Res., January 1, 2002; 62(2): 371 - 375. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. L.M. Poon, T. N. Leung, T. K. Lau, K. C.K. Chow, and Y.M. D. Lo Differential DNA Methylation between Fetus and Mother as a Strategy for Detecting Fetal DNA in Maternal Plasma Clin. Chem., January 1, 2002; 48(1): 35 - 41. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Widschwendter and P. A. Jones The Potential Prognostic, Predictive, and Therapeutic Values of DNA Methylation in Cancer : Commentary re: J. Kwong et al., Promoter Hypermethylation of Multiple Genes in Nasopharyngeal Carcinoma. Clin. Cancer Res., 8: 131-137, 2002, and H-Z. Zou et al., Detection of Aberrant p16 Methylation in the Serum of Colorectal Cancer Patients. Clin. Cancer Res., 8: 188-191, 2002. Clin. Cancer Res., January 1, 2002; 8(1): 17 - 21. [Full Text] [PDF]
|
|
|
|
|
|
H.-Z. Zou, B.-M. Yu, Z.-W. Wang, J.-Y. Sun, H. Cang, F. Gao, D. H. Li, R. Zhao, G.-G. Feng, and J. Yi Detection of Aberrant p16 Methylation in the Serum of Colorectal Cancer Patients Clin. Cancer Res., January 1, 2002; 8(1): 188 - 191. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Ueki, M. Toyota, H. Skinner, K. M. Walter, C. J. Yeo, J.-P. J. Issa, R. H. Hruban, and M. Goggins Identification and Characterization of Differentially Methylated CpG Islands in Pancreatic Carcinoma Cancer Res., December 1, 2001; 61(23): 8540 - 8546. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Hagen and T. R. DeMeester Esophageal adenocarcinoma Ann. Thorac. Surg., October 1, 2001; 72(4): 1430 - 1432. [Full Text] [PDF]
|
|
|
|
|
|
R. W. K. Chiu, L. L. M. Poon, T. K. Lau, T. N. Leung, E. M. C. Wong, and Y. M. D. Lo Effects of Blood-Processing Protocols on Fetal and Total DNA Quantification in Maternal Plasma Clin. Chem., September 1, 2001; 47(9): 1607 - 1613. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Silva, G. Dominguez, J. Silva, J. M. Garcia, A. Sanchez, O. Rodriguez, M. Provencio, P. Espana, and F. Bonilla Detection of Epithelial Messenger RNA in the Plasma of Breast Cancer Patients Is Associated with Poor Prognosis Tumor Characteristics Clin. Cancer Res., September 1, 2001; 7(9): 2821 - 2825. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. F Costello and C. Plass Methylation matters J. Med. Genet., May 1, 2001; 38(5): 285 - 303. [Abstract] [Full Text]
|
|