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)

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• 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

Peter H. Baenziger – pbaenzig@iupui.eduCenter for Computational Biology and Bioinformatics

Indiana University School of Medicine

Phosphorylation

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• 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

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.

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

5/6Peter 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

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.