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Disease Markers
Volume 28 (2010), Issue 4, Pages 241-251
http://dx.doi.org/10.3233/DMA-2010-0702

Alternative Splice Variants, a New Class of Protein Cancer Biomarker Candidates: Findings in Pancreatic Cancer and Breast Cancer with Systems Biology Implications

Gilbert S. Omenn,1,2 Anastasia K. Yocum,1,3 and Rajasree Menon1

1University of Michigan Center for Computational Medicine and Bioinformatics and Michigan Proteomics Alliance for Cancer Research, Ann Arbor, MI, USA
2Departments of Internal Medicine, Human Genetics and School of Public Health, University of Michigan, Ann Arbor, MI, USA
3Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA

Received 31 May 2010; Accepted 31 May 2010

Copyright © 2010 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Alternative splicing plays an important role in protein diversity without increasing genome size. Earlier thought to be uncommon, splicing appears to affect the majority of genes. Alternative splice variants have been detected at the mRNA level in many diseases. We have designed and demonstrated a discovery pipeline for alternative splice variant (ASV) proteins from tandem MS/MS datasets. We created a modified ECgene database with entries from exhaustive three-frame translation of Ensembl transcripts and gene models from ECgene, with periodic updates. The human database has 14 million entries; the mouse database, 10 million entries. We match MS/MS findings against these potential translation products to identify and quantify known and novel ASVs. In this review, we summarize findings and systems biology implications of biomarker candidates from a mouse model of human pancreatic ductal adenocarcinoma [28] and a mouse model of human Her2/neu-induced breast cancer [27]. The same approach is being applied to human tumors, plasma, and cell line studies of other cancers.