Abstract
Abstract: Predicting who will develop cancer and how the cancer will behave and respond to therapy after diagnosis are some of the potential benefits of the ongoing genetic revolution that can be envisioned within the next decade. Translational applications of genomic-based research efforts may actually precede the development of effective therapeutic agents that can exploit the vast amounts of data derived from these efforts. In the future, understanding the wealth of information generated by high-throughput molecular efforts and how it can be applied to clinical problems will likely be critical to the surgeon who guides the multidisciplinary care of the cancer patient. This review will discuss the advances in our understanding of the human genome (DNA), its derived transcriptome (RNA), and its translated proteome (proteins) and will focus on the translation of this information into routine clinical practice. In particular, we will focus on the potential for clinical application of microarray-based gene-expression profiling to the diagnosis, prognosis, and therapy of malignancies.
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REFERENCES
Lewin R. Proposal to sequence the human genome stirs debate. Science 1986; 232: 1598–600.
Lander ES, Linton LM, Birren B, et al. Initial sequencing and analysis of the human genome. Nature 2001; 409: 860–921.
Venter JC, Adams MD, Myers EW, et al. The sequence of the human genome. Science 2001; 291: 1304–51.
Saha S, Sparks AB, Rago C, et al. Using the transcriptome to annotate the genome. Nat Biotechnol 2002; 20: 508–12.
Adams MD, Celniker SE, Holt RA, et al. The genome sequence of Drosophila melanogaster . Science 2000; 287: 2185–95.
Genome sequence of the nematode C. elegans: a platform for investigating biology. The C. elegans Sequencing Consortium. Science 1998;282:2012–8.
Analysis of the genome sequence of the flowering plant Arabidop-sis thaliana Nature Science 2000;408:796 – 815.
Webb T. SNPs: can genetic variants control cancer susceptibility? J Natl Cancer Inst 2002; 94: 476–8.
Relling MV, Dervieux T. Pharmacogenetics and cancer therapy. Nat Rev Cancer 2001; 1: 99–108.
Srinivas PR, Kramer BS, Srivastava S. Trends in biomarker research for cancer detection. Lancet Oncol 2001; 2: 698–704.
Brock GJ, Huang TH, Chen CM, Johnson KJ. A novel technique for the identification of CpG islands exhibiting altered methylation patterns (ICEAMP). Nucleic Acids Res 2001; 29: E123.
Yan PS, Wei SH, Huang TH. Differential methylation hybridization using CpG island arrays. Methods Mol Biol 2002; 200: 87–100.
Suzuki H, Gabrielson E, Chen W, et al. A genomic screen for genes upregulated by demethylation and histone deacetylase inhibition in human colorectal cancer. Nat Genet 2002; 31: 141–9.
Su AI, Cooke MP, Ching KA, et al. Large-scale analysis of the human and mouse transcriptomes. Proc Natl Acad Sci U S A 2002; 99: 4465–70.
Quackenbush J. Computational analysis of microarray data. Nat Rev Genet 2001; 2: 418–27.
Ideker T, Galitski T, Hood L. A new approach to decoding life: systems biology. Annu Rev Genomics Hum Genet 2001; 2: 343–72.
Davidson EH, Rast JP, Oliveri P, et al. A genomic regulatory network for development. Science 2002; 295: 1669–78.
Graham TA, Weaver C, Mao F, et al. Crystal structure of a beta-catenin/Tcf complex. Cell 2000; 103: 885–96.
Sperling K. From proteomics to genomics. Electrophoresis 2001; 22: 2835–7.
Klose J. Protein mapping by combined isoelectric focusing and electrophoresis of mouse tissues. A novel approach to testing for induced point mutations in mammals. Humangenetik 1975; 26: 231–43.
O’Farrell PH. High resolution two-dimensional electrophoresis of proteins. J Biol Chem 1975; 250: 4007–21.
Scheele GA. Two-dimensional gel analysis of soluble proteins. Characterization of guinea pig exocrine pancreatic proteins. J Biol Chem 1975; 250: 5375–85.
Anderson L, Seilhamer J. A comparison of selected mRNA and protein abundances in human liver. Electrophoresis 1997; 18: 533–7.
Lee KH. Proteomics: a technology-driven and technology-limited discovery science. Trends Biotechnol 2001; 19: 217–22.
Agrawal D, Chen T, Irby R, et al. Osteopontin identified as lead marker of colon cancer progression, using pooled sample expression profiling. J Natl Cancer Inst 2002; 94: 513–21.
Giordano TJ, Shedden KA, Schwartz DR, et al. Organ-specific molecular classification of primary lung, colon, and ovarian adenocarcinomas using gene expression profiles. Am J Pathol 2001; 159: 1231–8.
Ramaswamy S, Tamayo P, Rifkin R, et al. Multiclass cancer diagnosis using tumor gene expression signatures. Proc Natl Acad Sci U S A 2001; 98: 15149–54.
Alizadeh AA, Ross DT, Perou CM, van de Rijn M. Towards a novel classification of human malignancies based on gene expression patterns. J Pathol 2001; 195: 41–52.
Su AI, Welsh JB, Sapinoso LM, et al. Molecular classification of human carcinomas by use of gene expression signatures. Cancer Res 2001; 61: 7388–93.
Bhattacharjee A, Richards WG, Staunton J, et al. Classification of human lung carcinomas by mRNA expression profiling reveals distinct adenocarcinoma subclasses. Proc Natl Acad Sci U S A 2001; 98: 13790–5.
Shipp MA, Ross KN, Tamayo P, et al. Diffuse large B-cell lymphoma outcome prediction by gene-expression profiling and supervised machine learning. Nat Med 2002; 8: 68–74.
Takahashi M, Rhodes DR, Furge KA, et al. Gene expression profiling of clear cell renal cell carcinoma: gene identification and prognostic classification. Proc Natl Acad Sci U S A 2001; 98: 9754–9.
West M, Blanchette C, Dressman H, et al. Predicting the clinical status of human breast cancer by using gene expression profiles. Proc Natl Acad Sci U S A 2001; 98: 11462–7.
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Yeatman, T.J. The Future of Cancer Management: Translating the Genome, Transcriptome, and Proteome. Ann Surg Oncol 10, 7–14 (2003). https://doi.org/10.1245/ASO.2003.05.031
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DOI: https://doi.org/10.1245/ASO.2003.05.031