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 Sean D. Mooney (Indiana University School of Medicine) –K22LM –R01LM –Grant from IU Biomedical Research Council, Indiana University, the Showalter Trust and the Indiana Genomics Initiative. Peter H. Baenziger – Center for Computational Biology and Bioinformatics Indiana University School of Medicine

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 –

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

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

5/6Peter H. Baenziger – 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

Conclusions 6/6Peter H. Baenziger – 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.