Charles M. Perou, PhD

2009-2010 BCRF Project:
Dr. Perou's previous work has shown that breast cancer is not a single disease, but instead, represents a series of diseases that includes the poor outcome ER-positive tumor group called the "Luminal B" subtype and the newly described "Claudin-low" subtype. His research is focused on identifying the causative genetic alterations that give rise to ER+/Luminal tumors, especially Luminal B tumors, and on determining the role of stem cells in their biology.

In the past years, his team identified a number of potentially causative Luminal B genetic events including gene mutation (TP53 and GATA3), and tumor DNA gains and losses. They have introduced many of these changes into cell lines and laboratory models and determined that most alter drug sensitivity. In addition, they have recently identified a new tumor phenotype called the "Claudin-low" subtype, which appears enriched for stem cell markers and that becomes more enriched following treatment. Many of these findings have prognostic and predictive significance, and thus, they are using these complex genomic data, along with classic clinical variables, to build predictive mathematical models for breast cancer patient outcomes that could assist in making therapeutic decisions.

Mid-Year Progress Report:
Dr. Perou's work has shown that breast cancer is not a single disease, but instead, represents a series of diseases that includes the poor outcome ER-positive tumor group called the "Luminal B" subtype, and the ER-negative "Claudin-low" subtype. This work is focused on identifying the causative genetic alterations that give rise to Luminal B and Claudin-low tumors, and on determining the role of stem cells in their biology. In the past years, the Perou team identified a number of causative Luminal B genetic events including gene mutations (TP53), tumor DNA gains (MYBL2) and losses (RB1). In addition, they identified a new tumor subtype/group called the "Claudin-low" subtype that appears enriched for stem cells, and which show features similar to the aggressive but rare, Metaplastic Carcinomas.

Recent progress has shown that human Claudin-low cell lines, and model Claudin-low tumors, are highly enriched for Tumor Initiating Cells (i.e. >50% of the cells within a tumor), which are the cells capable of forming new tumors. Dr. Perou and his colleagues are using these genomic data, including their new Claudin-low/stem cell signature, along with the other molecular factors (mutations) and classic clinical variables like tumor size, to build mathematical models to predict breast cancer patient outcomes that could assist in therapeutic decision making.

Bio:
Dr. Perou is a member of the Lineberger Comprehensive Cancer Center, the Carolina Center for Genome Sciences, and the Scientific Director of the UNC Genomics and Bioinformatics Core Facility. He received his Ph.D. in Cellular and Molecular Biology from the Department of Pathology at the University of Utah (1996) where he cloned and characterized the human Chediak-Higashi Syndrome gene. He next performed his postdoctoral training in the laboratory of David Botstein at Stanford University (1997-2000) where he began his genomic studies of human tumors using DNA microarrays. These genomic analyses resulted in the identification of novel subtypes of human breast tumors that predict patient survival times and response to therapy. Dr. Perou's laboratory at UNC is focused on using genomics, genetics, and animal models to decipher the underlying biology of the molecular subtypes of breast cancer, and then using this biological information to develop therapies that are specifically targeted against each of these distinct subtypes of breast cancer.