title: Innovations in proteomic profiling of cancers: alternative splice variants as a new class of cancer biomarker candidates and bridging of proteomics with structural biology.
abstract: Alternative splicing allows a single gene to generate multiple RNA transcripts which can be translated into functionally diverse protein isoforms. Current knowledge of splicing is derived mainly from RNA transcripts, with very little known about the expression level, 3D structures, and functional differences of the proteins. Splicing is a remarkable phenomenon of molecular and biological evolution. Studies which simply report up-regulation or down-regulation of protein or mRNA expression are confounded by the effects of mixtures of these isoforms. Besides understanding the net biological effects of the mixtures, we may be able to develop biomarker tests based on the observable differential expression of particular splice variants or combinations of splice variants in specific disease states. Here we review our work on differential expression of splice variant proteins in cancers and the feasibility of integrating proteomic analysis with structure-based conformational predictions of the differences between such isoforms.
authors.affiliation: Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109-2218, USA. gomenn@umich.edu
authors.forename: Gilbert S
authors.initials: GS
authors.lastname: Omenn
authors.forename: Rajasree
authors.initials: R
authors.lastname: Menon
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000737:chemistry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000737:chemistry; D009369:Neoplasms / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D020033:Protein Isoforms / Q000378:metabolism; D017434:Protein Structure, Tertiary; D040901:Proteomics; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D012334:RNA, Neoplasm
keywords: Cancer biomarkers; Computational modeling; Differential expression; Splicing