1. Is phosphorylation site disruption associated with cancer? Maricel G. Kann (University of Maryland, Baltimore County) Matthew E. Mort (Indiana University School of Medicine) Matthew Hahn (Indiana University) 1/6 Pedreg Radivojac (Indiana University) –NSF award DBI-0644017 Sean D. Mooney (Indiana University School of Medicine) –K22LM009135 –R01LM009722 –Grant from IU Biomedical Research Council, Indiana University, the Showalter Trust and the Indiana Genomics Initiative. Peter H. Baenziger – pbaenzig@iupui.edu Center for Computational Biology and Bioinformatics Indiana University School of Medicine

2. Phosphorylation 2/6 Serine, Threonine, and Tyrosine are phosphorylatable. –Kinases phosphorylate. –Phosphatases dephosphorylate. Phosphorylation affects signaling pathways. Kinase inhibitors such as Gleevec ® (imatinib mesylate) are important cancer treatment targets. Peter H. Baenziger – pbaenzig@iupui.edu

3. Phosphorylation 3/6Peter H. Baenziger – pbaenzig@iupui.edu S, T, or Y specifically targeted by kinases. DisPhos predicts phosphorylation on sites. Hypothesis: mutations may disrupt kinase and phosphatase target sites.

4. Do mutations of target amino acids disrupt phosphorylation sites? 4/6Peter H. Baenziger – pbaenzig@iupui.edu Somatic mutations from breast and colorectal cancer tumors Somatic mutations from kinase genes of tumors from many cancers ** * Random mutations

5. 5/6Peter H. Baenziger – pbaenzig@iupui.edu Do mutations of target amino acids disrupt phosphorylation sites? Somatic mutations from breast and colorectal cancer tumors Somatic mutations from kinase genes of tumors from many cancers

6. Conclusions 6/6Peter H. Baenziger – pbaenzig@iupui.edu Phosphorylation site disruption might be a mechanism in cancer. Phosphorylation site disruption may be a useful feature in mutation classification. See poster for more information.