Special Lecture

Splice Variant Proteins as a New Class of Cancer Biomarker Candidates

Gilbert S. Omenn, MD, PhD

The evolutionary development of alternative splice transcripts from protein-coding genes in multicellular organisms has greatly increased the complexity of gene expression and protein function. The splicing phenomenon and the evidence for differential expression of splice isoforms make descriptions of up-regulation and down-regulation of gene and protein expression quite simplistic. This presentation will include findings from mouse models of Kras-activated/Ink4a/arf deleted human pancreatic cancer and ERBB2-amplified breast cancers and from cultured human cancer cell lines, showing differential expression of splice variants of cancer-relevant genes and the mechanisms producing the splice variants. Our method and modified ECgene database could be used for many other studies. We have utilized the I-TASSER and QUARK conformation predicting algorithms of Yang Zhang to characterize the structural differences and likely functional consequences for pairs of cogent splice variants. We have also contributed to the Chromosome 17 project of the Chromosome-centric Human Proteome Project, focusing on ERBB2-amplified breast cancers.