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The grand challenge to decipher the cancer proteome

Abstract

The quest to decipher protein alterations in cancer has spanned well over half a century. The vast dynamic range of protein abundance coupled with a plethora of isoforms and disease heterogeneity have been formidable challenges. Progress in cancer proteomics has substantially paralleled technological developments. Advances in analytical techniques and the implementation of strategies to de-complex the proteome into manageable components have allowed proteins across a wide dynamic range to be explored. The massive amounts of data that can currently be collected through proteomics allow the near-complete definition of cancer subproteomes, which reveals the alterations in signalling and developmental pathways. This allows the discovery of predictive biomarkers and the annotation of the cancer genome based on proteomic findings. There remains a considerable need for infrastructure development and the organized collaborative efforts to efficiently mine the cancer proteome.

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Figure 1: Increased resolving power of proteomics technologies as applied to serum and plasma.
Figure 2: Depth of analysis of the plasma proteome.
Figure 3: Quantitative profiling of proteins in tumour tissue using a modified SILAC strategy32.

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Acknowledgements

The authors would like to thank colleagues in the Molecular Diagnostics Program at FHCRC for stimulating discussions.

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Correspondence to Samir Hanash.

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DATABASES

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FURTHER INFORMATION

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Global Proteome Machine

Human Protein Atlas

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Glossary

2D PAGE

A process of separating proteins in gels based on their charge and molecular mass.

Electrospray ionization

ESI. A mass spectrometry method to ionize macromolecules or peptides by electrospray leading to their identification.

Fluorescence difference gel electrophoresis

DIGE. A method that labels protein samples with fluorescent dyes before electrophoresis.

Immobilized pH gradients

IPG. A process of generating a pH gradient by immobilizing gradient chemicals (immobilines) in the acrylamide matrix.

Lectin

A sugar-binding protein that is specific for the sugar moieties it binds.

Matrix-assisted laser desorption ionization

MALDI. A mass spectrometry method to ionize proteins and peptides deposited in a matrix leading to their identification.

Multiple reaction monitoring

MRM. A technique that targets multiple specific peptides for their quantification by mass spectrometry.

Secretome

The ensemble of proteins released by cells into the extracellular environment.

Stable isotope labelling by amino acids in cell culture

SILAC. A method for non-radioactive labelling of proteins in culture based on the uptake of labelled amino acids.

Tandem mass spectrometry

MS/MS. A two-stage separation process in mass spectrometry with fragmentation in-between allowing identification of the precursor.

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Hanash, S., Taguchi, A. The grand challenge to decipher the cancer proteome. Nat Rev Cancer 10, 652–660 (2010). https://doi.org/10.1038/nrc2918

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