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1 Department of Pathology, University of Utah School of Medicine, 30 North 1900 East, Salt Lake City, UT 84132.
aAuthor for correspondence. Fax 801-581-4517; e-mail phil.bernard{at}path.utah.edu.
Background: Advances in the biological sciences and technology are providing molecular targets for diagnosing and treating cancer. Current classifications in surgical pathology for staging malignancies are based primarily on anatomic features (e.g., tumor-node-metastasis) and histopathology (e.g., grade). Microarrays together with clustering algorithms are revealing a molecular diversity among cancers that promises to form a new taxonomy with prognostic and, more importantly, therapeutic significance. The challenge for pathology will be the development and implementation of these molecular classifications for routine clinical practice.
Approach: This article discusses the benefits, challenges, and possibilities for solid-tumor profiling in the clinical laboratory with an emphasis on DNA-based PCR techniques.
Content: Molecular markers can be used to provide accurate prognosis and to predict response, resistance, or toxicity to therapy. The diversity of genomic alterations involved in malignancy necessitates a variety of assays for complete tumor profiling. Some new molecular classifications of tumors are based on gene expression, requiring a paradigm shift in specimen processing to preserve the integrity of RNA for analysis. More stable markers (i.e., DNA and protein) are readily handled in the clinical laboratory. Quantitative real-time PCR can determine gene duplications or deletions. Furthermore, melting curve analysis immediately after PCR can identify small mutations, down to single base changes. These techniques are becoming easier and faster and can be multiplexed. Real-time PCR methods are a favorable option for the analysis of cancer markers.
Summary: There is a need to translate recent discoveries in oncology research into clinical practice. This requires objective, robust, and cost-effective molecular techniques for clinical trials and, eventually, routine use. Real-time PCR has attractive features for tumor profiling in the clinical laboratory.
The following articles in journals at HighWire Press have cited this article:
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I. G. Yulug and B. Gur-Dedeoglu Functional genomics in translational cancer research: focus on breast cancer Brief Funct Genomic Proteomic, March 7, 2008; (2008) eln009v1. [Abstract] [Full Text] [PDF] |
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A. L. Carvalho, C. Jeronimo, M. M. Kim, R. Henrique, Z. Zhang, M. O. Hoque, S. Chang, M. Brait, C. S. Nayak, W.-W. Jiang, et al. Evaluation of Promoter Hypermethylation Detection in Body Fluids as a Screening/Diagnosis Tool for Head and Neck Squamous Cell Carcinoma Clin. Cancer Res., January 1, 2008; 14(1): 97 - 107. [Abstract] [Full Text] [PDF] |
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S. Huang, J. Salituro, N. Tang, K.-C. Luk, J. Hackett Jr, P. Swanson, G. Cloherty, W.-B. Mak, J. Robinson, and K. Abravaya Thermodynamically modulated partially double-stranded linear DNA probe design for homogeneous real-time PCR Nucleic Acids Res., August 13, 2007; 35(16): e101 - e101. [Abstract] [Full Text] [PDF] |
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E. Retamales, L. Rodriguez, L. Guzman, F. Aguayo, M. Palma, C. Backhouse, J. Argandona, E. Riquelme, and A. Corvalan Analytical Detection of Immunoglobulin Heavy Chain Gene Rearrangements in Gastric Lymphoid Infiltrates by Peak Area Analysis of the Melting Curve in the LightCycler System J. Mol. Diagn., July 1, 2007; 9(3): 351 - 357. [Abstract] [Full Text] [PDF] |
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L. A. Wagner, C. J. Christensen, D. M. Dunn, G. J. Spangrude, A. Georgelas, L. Kelley, M. S. Esplin, R. B. Weiss, and G. J. Gleich EGO, a novel, noncoding RNA gene, regulates eosinophil granule protein transcript expression Blood, June 15, 2007; 109(12): 5191 - 5198. [Abstract] [Full Text] [PDF] |
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J. S. Ellis, J. W. Smith, S. Braham, M. Lock, K. Barlow, and M. C. Zambon Design and Validation of an H5 TaqMan Real-Time One-Step Reverse Transcription-PCR and Confirmatory Assays for Diagnosis and Verification of Influenza A Virus H5 Infections in Humans J. Clin. Microbiol., May 1, 2007; 45(5): 1535 - 1543. [Abstract] [Full Text] [PDF] |
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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] |
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J. Stenman, A. Paju, O. Rissanen, T. Tenkanen, C. Haglund, J. Rasanen, J. Salo, U.-H. Stenman, and A. Orpana Targeted Gene-Expression Analysis by Genome-Controlled Reverse Transcription-PCR Clin. Chem., November 1, 2006; 52(11): 1988 - 1996. [Abstract] [Full Text] [PDF] |
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N. Xenidis, M. Perraki, M. Kafousi, S. Apostolaki, I. Bolonaki, A. Stathopoulou, K. Kalbakis, N. Androulakis, C. Kouroussis, T. Pallis, et al. Predictive and Prognostic Value of Peripheral Blood Cytokeratin-19 mRNA-Positive Cells Detected by Real-Time Polymerase Chain Reaction in Node-Negative Breast Cancer Patients J. Clin. Oncol., August 10, 2006; 24(23): 3756 - 3762. [Abstract] [Full Text] [PDF] |
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S. Schulz, T. Hyslop, J. Haaf, C. Bonaccorso, K. Nielsen, M. E. Witek, R. Birbe, J. Palazzo, D. Weinberg, and S. A. Waldman A Validated Quantitative Assay to Detect Occult Micrometastases by Reverse Transcriptase-Polymerase Chain Reaction of Guanylyl Cyclase C in Patients with Colorectal Cancer Clin. Cancer Res., August 1, 2006; 12(15): 4545 - 4552. [Abstract] [Full Text] [PDF] |
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Y. Li, D. Elashoff, M. Oh, U. Sinha, M. A.R. St John, X. Zhou, E. Abemayor, and D. T. Wong Serum Circulating Human mRNA Profiling and Its Utility for Oral Cancer Detection J. Clin. Oncol., April 10, 2006; 24(11): 1754 - 1760. [Abstract] [Full Text] [PDF] |
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H.-z. Luo, Z.-g. Zhou, L. Yang, Y.-y. Yu, C. Tian, B. Zhou, X.-L. Zheng, Q.-j. Xia, Y. Li, and R. Wang Clinicopathologic and Prognostic Significance of MMP-7 (Matrilysin) Expression in Human Rectal Cancer Jpn. J. Clin. Oncol., December 1, 2005; 35(12): 739 - 744. [Abstract] [Full Text] [PDF] |
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E. Kierzek, A. Ciesielska, K. Pasternak, D. H. Mathews, D. H. Turner, and R. Kierzek The influence of locked nucleic acid residues on the thermodynamic properties of 2'-O-methyl RNA/RNA heteroduplexes Nucleic Acids Res., September 9, 2005; 33(16): 5082 - 5093. [Abstract] [Full Text] [PDF] |
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W. E. Highsmith Jr SNPs for Sale. Cheap! Clin. Chem., August 1, 2004; 50(8): 1296 - 1298. [Full Text] [PDF] |
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R. Parihar, P. Nadella, A. Lewis, R. Jensen, C. De Hoff, J. E. Dierksheide, A. M. VanBuskirk, C. M. Magro, D. C. Young, C. L. Shapiro, et al. A Phase I Study of Interleukin 12 with Trastuzumab in Patients with Human Epidermal Growth Factor Receptor-2-Overexpressing Malignancies: Analysis of Sustained Interferon {gamma} Production in a Subset of Patients Clin. Cancer Res., August 1, 2004; 10(15): 5027 - 5037. [Abstract] [Full Text] [PDF] |
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S. M. Myers and L. M. Mulligan The RET Receptor Is Linked to Stress Response Pathways Cancer Res., July 1, 2004; 64(13): 4453 - 4463. [Abstract] [Full Text] [PDF] |
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A. Stahlberg, J. Hakansson, X. Xian, H. Semb, and M. Kubista Properties of the Reverse Transcription Reaction in mRNA Quantification Clin. Chem., March 1, 2004; 50(3): 509 - 515. [Abstract] [Full Text] [PDF] |
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A. K. Cashion, C. J. Driscoll, and O. Sabek Emerging Genetic Technologies in Clinical and Research Settings Biol Res Nurs, January 1, 2004; 5(3): 159 - 167. [Abstract] [PDF] |
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E. Floyd and T. M. Mcshane Development and Use of Biomarkers in Oncology Drug Development Toxicol Pathol, January 1, 2004; 32(1_suppl): 106 - 115. [Abstract] [PDF] |
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A. Stathopoulou, A. Gizi, M. Perraki, S. Apostolaki, N. Malamos, D. Mavroudis, V. Georgoulias, and E. S. Lianidou Real-Time Quantification of CK-19 mRNA-Positive Cells in Peripheral Blood of Breast Cancer Patients Using the Lightcycler System Clin. Cancer Res., November 1, 2003; 9(14): 5145 - 5151. [Abstract] [Full Text] [PDF] |
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M. B. Grace, C. B. McLeland, S. J. Gagliardi, J. M. Smith, W. E. Jackson III, and W. F. Blakely Development and Assessment of a Quantitative Reverse Transcription-PCR Assay for Simultaneous Measurement of Four Amplicons Clin. Chem., September 1, 2003; 49(9): 1467 - 1475. [Abstract] [Full Text] [PDF] |
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R. Soong and A. Ladanyi Improved Indicators for Assessing the Reliability of Detection and Quantification by Kinetic PCR Clin. Chem., June 1, 2003; 49(6): 973 - 976. [Full Text] [PDF] |
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