Abstract
Introduction The functional consequences of genetic and epigenetic changes that occur during tumor development and progression are mediated through protein alterations, which in turn account for the hallmarks of cancer, including uncontrolled proliferation, and tissue invasion and metastasis. Our current knowledge of the proteome and the spectrum of protein changes that occur in cancer and their functional consequences remain limited (1). We are challenged by the complexity of the proteome stemming from numerous post-translational modifications and the multitude of subcellular compartments in which proteins reside or traffic. As a result, most proteomic investigations have tackled a particular feature or component of the proteome, whether in cells, tissues, or biological fluids (Table 7.1). The emphasis of cancer proteomic studies has been on the identification of diagnostic, prognostic, or predictive markers, the identification of novel therapeutic targets, elucidation of signaling pathways regulated by oncogenes, and other genetic alterations that occur in cancer. Some of the progress made to date and the technologies utilized are highlighted in this chapter. Proteomic technologies: mass spectrometry Currently the workhorse for proteomic discovery studies is mass spectrometry, which has evolved from a tool to identify and characterize isolated proteins or for mass peak profiling of more complex protein mixtures, as in the application of matrix-assisted laser desorption ionization (MALDI) to clinical samples, to a high-performance platform for interrogating proteomes by matching mass spectra to sequence databases to derive protein identifications (15). The parallel development of electrospray ionization mass spectrometry for protein identification coupled with various pre-fractionation and separation schemes has allowed quantitative analysis of an ever-increasing number of proteins from cells, tissues, and biological fluids. Mass spectrometers currently available have significantly increased sensitivity and scan speed (16). As a result, identification of the major protein form of virtually all proteins translated from expressed genes in a cancer cell population and the comprehensive analysis of the serum and plasma proteome across seven or more logs of protein abundance have become achievable (17). However, such coverage of the proteome using mass spectrometry is achieved with low throughput. The massive amount of data produced necessitate intense informatics and statistical analysis to identify protein alterations associated with a disease state such as cancer.
Original language | English (US) |
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Title of host publication | Molecular Oncology |
Subtitle of host publication | Causes of Cancer and Targets for Treatment |
Publisher | Cambridge University Press |
Pages | 52-57 |
Number of pages | 6 |
ISBN (Electronic) | 9781139046947 |
ISBN (Print) | 9780521876629 |
DOIs | |
State | Published - Jan 1 2015 |
ASJC Scopus subject areas
- General Medicine