DR-223 Identification of Mutations in Signaling Proteins in Metastatic Breast Cancer Cells

Cancer-related signaling pathways frequently involve protein kinase C (PKC), a prominent enzyme that phosphorylates alpha-tubulin, a building block of microtubules.  Phosphorylated alpha-tubulin causes human breast cells to acquire metastatic potential, whereas with non-phosphorylated alpha-tubulin, cells are hyperproliferative, as shown in an animal model.  Genomic sequences of primary tumors in publicly available databases showed that alpha-tubulin acquires mutations at the PKC phosphorylation site that are primarily blocking mutations, and were therefore consistent with the genomic samples were from primary tumors.  With the HMF dataset, we will examine data from breast lesions that are authentically metastatic, enabling validation of alpha-tubulin as a bio-marker for predicting metastatic potential and thereby aiding in cancer diagnostics. More generally, we will be alert to novel recurring mutations in other genes that have not yet been studied.

Susan Rotenberg, Queens College of The City University of New York, United States of America