Abstract

Genome-Scale Protein Expression Analysis of Individual Solid Tumors

Metodi Metodiev, Biological Safety Officer, University of Essex

Present diagnostic procedures and therapeutic strategies solid tumours rely on the detection and targeting of specific marker molecules to classify the tumour and to design an efficient therapy. Examples for such markers/targets, in the case of breast cancer, are the oestrogen receptor (ER), progesterone receptor (PgR), and the Erb2/Her2 molecule, a receptor tyrosine protein kinase that is overexpressed in a subset of breast cancers. There are number of treatment options for tumours that express the ER, PgR or Her2 receptors, however up to 20 percent of the newly diagnosed cases belong to a subset, which is negative for all three of the receptor molecules. This presentation will discuss applications of high-resolution hybrid mass spectrometry for quantitative genome-scale studies of protein abundance and post-translational modifications. The current state-of-the-art technology for large-scale proteome analysis of individual solid tumours is discussed. Case studies from experiments with triple-negative breast and colorectal tumours illustrating the capability of the proteome-based strategies are presented, as well as mechanistic investigations in cultured cells that have been informed by tumour proteomics and focus on specific phosphorylation hotspots and protein interactions of the tumour suppressor Scribble.