BAP1 and involvement in Mesothelioma, CMML, Uveal (eye) melanoma

BAP1 is a de-ubiquitinating enzyme (DUB) found in the nucleus

BAP1 has many roles within the cell

Developmental problems in mice

BAP1 mutations are found in many human cancers

• Breast

• Lung

• Skin

• Kidney

• Prostate

• Ovary

• Colorectal

• Pancreatic

Hereditary BAP1 +/- predisposes humans to certain cancers

Mesothelioma

• Leukemia (CMML)

Uveal Melanoma

BAP1 KO Mice Enlarged d spleens

Excess White Blood Cells

Low Platelet d d and Red Blood d Cell Count

Chronic Myelomonocytic Leukemia (CMML)

Inhalation of asbestos fibers canlead to mesothelioma

Surgery Chemotherapy Radiation

Uveal melanomas can be treated with cutting-edge radiosurgery

References• Dieckmann, K., Georg, D., Zehetmayer, M., Bogner, J., Georgopoulos, M., and Pötter, R. (2003). LINAC based stereotactic radiotherapy

of uveal melanoma: 4 years clinical experience. Radiotherapy and Oncology, Volume 67, Issue 2, Pages 199–206• Ladanyi, M., Zauderer, M., Krug, L., Ito, T., McMillan, R., Bott, M., and Giancotti, F. (2012).• New Strategies in Pleural Mesothelioma: BAP1 and NF2 as Novel Targets for Therapeutic Development and Risk Assessment. Clin

Cancer Res , vol. 18 no. 17 4485-4490 • Dey, A., Bakalarski, C. E., Wu, J., Phu, L., Katavolos, P., LaFave, L. M., . . . Lill, J. R. (2012). Loss of the tumor suppressor BAP1 causes

myeloid transformation. Science (New York, N.Y.), 337(6101), 1541-1546. doi:10.1126/science.1221711• White, A., & Harper, J. (2012). Emerging anatomy of the BAP1 tumor suppressor system. Science, 337(6101), 1463-1464.

doi:10.1126/science.1228463• Abdel-Wahab, O., & Dey, A. (2013). The ASXL-BAP1 axis: New factors in myelopoiesis, cancer and epigenetics. Leukemia, 27(1), 10-15.

doi:10.1038/leu.2012.288• Testa, J. R., Trusa, S., Hesdorffer, M., Nasu, M., Powers, A., Rivera, Z., . . . Pass, H. I. (2011). Germline BAP1 mutations predispose to

malignant mesothelioma. Nature Genetics, 43(10), 1022-U140. doi:10.1038/ng.912• www.asbestos.com• http://www.vidaza.com/patient/understanding-vidaza.aspx