Genomic and proteomic advances in gastric cancer

Abstract

The "omic" revolution has affected every discipline in medicine and the life sciences. Gastric cancer is no exception to this phenomenon, with significant publications in genomics, proteomics, transcriptomics, and metabolomics appearing in the literature over recent years. In this chapter, we focus on some of the major advances in gastric cancer research uncovered by the availability of new technologies in the areas of genomics and proteomics. We are cognizant that there is no easier way to date a written piece of work than to write about novel technologies. Indeed, the pace of technology at this time makes it inevitable that by the time of publication the technology has moved forward. Our objective in this chapter is to highlight the principles of existing technologies and concentrate on how these have been used to advance our understanding or management of gastric cancer. Given the disparate technologies that are discussed, we have divided the chapter into two broad sections. The first concentrates on genomics and high-throughput nucleic acid-based technologies, whereas the second deals with proteomics and the large-scale measurements of proteins or peptides. Although these high-throughput technologies have significant advantages over traditional discovery platforms that have historically adopted a single gene or protein approach, a common issue faced by both platforms is how best to interpret the large amounts of data generated by these studies. This has led to the evolution of a pivotal specialist in this area termed the bioinformatician. This term has different meanings according to the context of use and will be discussed further in the section "Bioinformatic Analysis of Genomic Data." The molecular biology revolution of the 1970s and beyond has led to a cell-centric view of cancer in which oncogenes and tumor suppressor genes operating in a single cell are thought to be deterministic of cancer. Another facet of malignancy is the reemerging concept of cancer that was postulated in the nineteenth century by Paget which also included the dynamic interplay between a malignant epithelial cell and the tumor microenvironment (Paget 1889). The advent of high-throughput technologies has led to an evolving holistic view of cancer by allowing the simultaneous evaluation of thousands of products (genes or proteins) derived from multicellular tissues. The complexity of this relationship has become apparent given the multitude of gene or protein expression changes observed in cancer tissue. The challenge has been to determine which cells are expressing the molecules of interest to enable downstream experiments. These concepts are expanded in subsequent sections of the chapter and hopefully will enable an understanding of the current promises and limitations of many of these technologies with respect to gastric cancer. © 2009 Springer Science + Business Media, LLC. All rights reserved.