Alternative splice variants, a new class of protein cancer biomarker candidates: findings in pancreatic cancer and breast cancer with systems biology implications.
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.
Omenn
Gilbert S
GS
University of Michigan Center for Computational Medicine and Bioinformatics and Michigan Proteomics Alliance for Cancer Research, Ann Arbor, MI 48109-2218, USA. gomenn@umich.edu
Yocum
Anastasia K
AK
Menon
Rajasree
R
D000595:Amino Acid Sequence; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000175:diagnosis*; D018734:Genes, erbB-2; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010190:Pancreatic Neoplasms / Q000175:diagnosis*; D051381:Rats; D049490:Systems Biology; D053719:Tandem Mass Spectrometry
D014408:Biomarkers, Tumor