| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Regular Articles |
1 Breast Cancer Program, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, and Departments of 2 Surgery, 3 Clinical Trials and Biometry, and 4 Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland
If detected early, breast cancer is eminently curable. To detect breast cancer in samples with little cellularity, a high level of sensitivity is needed. Tumor-specific promoter hypermethylation has provided such a valuable tool for detection of cancer cells in biological samples. To accurately assess promoter hypermethylation for many genes simultaneously in small samples, we developed a novel method, quantitative multiplex-methylation-specific PCR (QM-MSP). QM-MSP is highly sensitive (1 in 104–105 copies of DNA) and linear over 5 orders of magnitude. For RASSF1A, TWIST, Cyclin D2, and HIN1, we observed significant differences in both the degree (P < 0.003) and incidence (P < 0.02) of hypermethylation between normal and malignant breast tissues. Evaluation of the cumulative hypermethylation of the four genes within each sample revealed a high level of sensitivity (84%) and specificity (89%) of detection of methylation. We demonstrate the application of this technique for detecting hypermethylated RASSF1A, TWIST, Cyclin D2, HIN1, and RARB in 50–1000 epithelial cells collected from breast ducts during endoscopy or by lavage. Such an approach could be used in a variety of small samples derived from different tissues, with these or different biomarkers to enhance detection of malignancy.
This article has been cited by other articles:
|
|
 |
|
  P.-K. Lo, H. Watanabe, P.-C. Cheng, W. W. Teo, X. Liang, P. Argani, J. S. Lee, and S. Sukumar MethySYBR, a Novel Quantitative PCR Assay for the Dual Analysis of DNA Methylation and CpG Methylation Density J. Mol. Diagn., September 1, 2009; 11(5): 400 - 414. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. J. Bailey, H. Easwaran, Y. Zhang, E. Griffiths, S. A. Belinsky, J. G. Herman, S. B. Baylin, H. E. Carraway, and T.-H. Wang MS-qFRET: A quantum dot-based method for analysis of DNA methylation Genome Res., August 1, 2009; 19(8): 1455 - 1461. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. SAKAKURA, T. HAMADA, K. MIYAGAWA, M. NISHIO, A. MIYASHITA, H. NAGATA, H. IDA, S. YAZUMI, E. OTSUJI, T. CHIBA, et al. Quantitative Analysis of Tumor-derived Methylated RUNX3 Sequences in the Serum of Gastric Cancer Patients Anticancer Res, July 1, 2009; 29(7): 2619 - 2625. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Fackler, A. Rivers, W. W. Teo, A. Mangat, E. Taylor, Z. Zhang, S. Goodman, P. Argani, R. Nayar, B. Susnik, et al. Hypermethylated Genes as Biomarkers of Cancer in Women with Pathologic Nipple Discharge Clin. Cancer Res., June 1, 2009; 15(11): 3802 - 3811. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Dietrich, R. Lesche, R. Tetzner, M. Krispin, J. Dietrich, W. Haedicke, M. Schuster, and G. Kristiansen Analysis of DNA Methylation of Multiple Genes in Microdissected Cells From Formalin-fixed and Paraffin-embedded Tissues J. Histochem. Cytochem., May 1, 2009; 57(5): 477 - 489. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. N. Vasilatos, G. Broadwater, W. T. Barry, J. C. Baker Jr., S. Lem, E. C. Dietze, G. R. Bean, A. D. Bryson, P. G. Pilie, V. Goldenberg, et al. CpG Island Tumor Suppressor Promoter Methylation in Non-BRCA-Associated Early Mammary Carcinogenesis Cancer Epidemiol. Biomarkers Prev., March 1, 2009; 18(3): 901 - 914. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Zhang, K. D. Meyer, and L. Zhang Fetal Exposure to Cocaine Causes Programming of Prkce Gene Repression in the Left Ventricle of Adult Rat Offspring Biol Reprod, March 1, 2009; 80(3): 440 - 448. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Chai and R. E. Brown Field Effect in Cancer-An Update Ann. Clin. Lab. Sci., January 1, 2009; 39(4): 331 - 337. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. H. Gort, K. P.M. Suijkerbuijk, S. M. Roothaan, V. Raman, M. Vooijs, E. van der Wall, and P. J. van Diest Methylation of the TWIST1 Promoter, TWIST1 mRNA Levels, and Immunohistochemical Expression of TWIST1 in Breast Cancer Cancer Epidemiol. Biomarkers Prev., December 1, 2008; 17(12): 3325 - 3330. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. P. M. Suijkerbuijk, M. J. Fackler, S. Sukumar, C. H. van Gils, T. van Laar, E. van der Wall, M. Vooijs, and P. J. van Diest Methylation is less abundant in BRCA1-associated compared with sporadic breast cancer Ann. Onc., November 1, 2008; 19(11): 1870 - 1874. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Euhus, D. Bu, S. Milchgrub, X.-J. Xie, A. Bian, A. M. Leitch, and C. M. Lewis DNA Methylation in Benign Breast Epithelium in Relation to Age and Breast Cancer Risk Cancer Epidemiol. Biomarkers Prev., May 1, 2008; 17(5): 1051 - 1059. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Shivapurkar, V. Stastny, Y. Xie, C. Prinsen, E. Frenkel, B. Czerniak, F. B. Thunnissen, J. D. Minna, and A. F. Gazdar Differential Methylation of a Short CpG-Rich Sequence within Exon 1 of TCF21 Gene: A Promising Cancer Biomarker Assay Cancer Epidemiol. Biomarkers Prev., April 1, 2008; 17(4): 995 - 1000. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Wu, M. J. Fackler, M. K. Halushka, D. W. Molavi, M. E. Taylor, W. W. Teo, C. Griffin, J. Fetting, N. E. Davidson, A. M. De Marzo, et al. Heterogeneity of Breast Cancer Metastases: Comparison of Therapeutic Target Expression and Promoter Methylation Between Primary Tumors and Their Multifocal Metastases Clin. Cancer Res., April 1, 2008; 14(7): 1938 - 1946. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. S. Gustafson Locked Nucleic Acids Can Enhance the Analytical Performance of Quantitative Methylation-Specific Polymerase Chain Reaction J. Mol. Diagn., January 1, 2008; 10(1): 33 - 42. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Dahl and P. Guldberg A ligation assay for multiplex analysis of CpG methylation using bisulfite-treated DNA Nucleic Acids Res., December 18, 2007; 35(21): e144 - e144. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. P. M. Suijkerbuijk, E. van der Wall, and P. J. van Diest Oxytocin: bringing magic into nipple aspiration Ann. Onc., October 1, 2007; 18(10): 1743 - 1744. [Full Text] [PDF]
|
|
|
|
|
|
D. M. Euhus, D. Bu, R. Ashfaq, X.-J. Xie, A. Bian, A. M. Leitch, and C. M. Lewis Atypia and DNA Methylation in Nipple Duct Lavage in Relation to Predicted Breast Cancer Risk Cancer Epidemiol. Biomarkers Prev., September 1, 2007; 16(9): 1812 - 1821. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Munson, J. Clark, K. Lamparska-Kupsik, and S. S. Smith Recovery of bisulfite-converted genomic sequences in the methylation-sensitive QPCR Nucleic Acids Res., May 14, 2007; 35(9): 2893 - 2903. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. F.G. de Maat, N. Umetani, E. Sunami, R. R. Turner, and D. S.B. Hoon Assessment of Methylation Events during Colorectal Tumor Progression by Absolute Quantitative Analysis of Methylated Alleles Mol. Cancer Res., May 1, 2007; 5(5): 461 - 471. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Zhang, A. Darwanto, T. A. Linkhart, L. C. Sowers, and L. Zhang Maternal Cocaine Administration Causes an Epigenetic Modification of Protein Kinase C{epsilon} Gene Expression in Fetal Rat Heart Mol. Pharmacol., May 1, 2007; 71(5): 1319 - 1328. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. M. Coyle, X.-J. Xie, C. M. Lewis, D. Bu, S. Milchgrub, and D. M. Euhus Role of Physical Activity in Modulating Breast Cancer Risk as Defined by APC and RASSF1A Promoter Hypermethylation in Nonmalignant Breast Tissue Cancer Epidemiol. Biomarkers Prev., February 1, 2007; 16(2): 192 - 196. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Visvanathan, S. Sukumar, and N. E. Davidson Epigenetic Biomarkers and Breast Cancer: Cause for Optimism. Clin. Cancer Res., November 15, 2006; 12(22): 6591 - 6593. [Full Text] [PDF]
|
|
|
|
|
|
Y. C. Antill, G. Mitchell, S. A. Johnson, L. Devereux, A. Milner, K.-A. Phillips, and I. G. Campbell Loss of Heterozygosity Analysis in Ductal Lavage Samples from BRCA1 and BRCA2 Carriers: A Cautionary Tale. Cancer Epidemiol. Biomarkers Prev., July 1, 2006; 15(7): 1396 - 1398. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. C. Lau, E. Raja, M. Salto-Tellez, Q. Liu, K. Ito, M. Inoue, T. C. Putti, M. Loh, T. K. Ko, C. Huang, et al. RUNX3 Is Frequently Inactivated by Dual Mechanisms of Protein Mislocalization and Promoter Hypermethylation in Breast Cancer. Cancer Res., July 1, 2006; 66(13): 6512 - 6520. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Fackler, K. Malone, Z. Zhang, E. Schilling, E. Garrett-Mayer, T. Swift-Scanlan, J. Lange, R. Nayar, N. E. Davidson, S. A. Khan, et al. Quantitative multiplex methylation-specific PCR analysis doubles detection of tumor cells in breast ductal fluid. Clin. Cancer Res., June 1, 2006; 12(11): 3306 - 3310. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Cairns Serum-Based Detection of Gene Hypermethylation in Cancers of the Breast and Ovary Am. Assoc. Cancer Res. Educ. Book, April 1, 2006; 2006(1): 202 - 204. [Full Text] [PDF]
|
|
|
|
 |
|
 C J Fabian, B F Kimler, M S Mayo, and S A Khan Breast-tissue sampling for risk assessment and prevention Endocr. Relat. Cancer, June 1, 2005; 12(2): 185 - 213. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Lehmann, I. Berg-Ribbe, L. U. Wingen, K. Brakensiek, T. Becker, J. Klempnauer, B. Schlegelberger, H. Kreipe, and P. Flemming Distinct Methylation Patterns of Benign and Malignant Liver Tumors Revealed by Quantitative Methylation Profiling Clin. Cancer Res., May 15, 2005; 11(10): 3654 - 3660. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Krop, A. Player, A. Tablante, M. Taylor-Parker, J. Lahti-Domenici, J. Fukuoka, S. K. Batra, N. Papadopoulos, W. G. Richards, D. J. Sugarbaker, et al. Frequent HIN-1 Promoter Methylation and Lack of Expression in Multiple Human Tumor Types Mol. Cancer Res., September 1, 2004; 2(9): 489 - 494. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
