Charles M. Perou, PhD
2012-2013 BCRF Project:
(made possible by generous support from Susan Hertog)
May Goldman Shaw Distinguished Professor of Molecular Oncology Research
Professor of Genetics & Pathology
Lineberger Comprehensive Cancer Center
University of North Carolina
Chapel Hill, North Carolina
Dr. Perou's seminal work has shown that breast cancer is not a single disease, but instead, represents a series of diseases that include the more favorable prognosis luminal A subtype and multiple worse prognosis subtypes including the luminal B, HER2 positive (HER2+), basal-like and claudin-low groups. His work is focused on identifying the causative genetic alterations that give rise to these poor prognosis subtypes through their continued use of multiple genomic and genetic technologies including DNA microarrays, RNA-sequencing and genome sequencing.
Dr. Perou's team has identified numerous possible causative lesions in these aggressive tumor subtypes and is adapting these changes in laboratory models for therapeutic testing. In addition, it is likely that cancer stem cells may exist within some of these subtypes, for which Dr. Perou's team is isolating these cells and functionally and genetically characterizing them. Lastly, these new data, including somatic mutations, along with a library of ~500 expression modules, ~600 DNA copy number regions of change and the standard clinical variables (TNM), are now being used to build ever better statistical models that may more accurately predict breast cancer patient outcomes and response to therapy.
Mid-year Progress: Dr. Perou's team continues to be focused on identifying the causative genetic alterations that give rise to poor prognosis subtypes of breast cancer, such as luminal B, HER2-positive, basal-like and Claudin-low groups, through the use of genomic and proteomic technologies. They are continuing to identify likely subtype-causative lesions in these aggressive tumor subtypes, for example the loss of TP53, RB1, and BRCA1 in basal-like tumors, which are also events that are commonly observed in serous ovarian cancers. The similarity between breast basal-like and ovarian cancers also extends to other aspects of the tumor genome, thus suggesting that these two tumor types might share an important common biology.
In addition, Dr. Perou's data suggests that cancer stem cells exist within some of these disease subtypes, especially basal-like and Claudin-low breast cancers. The team is isolating these potential stem cells and functionally characterizing them. Lastly, these new genomic and genetic data continue to be used to build ever better statistical predictors of patient outcomes and response to therapy, including predictors of endocrine and chemotherapy benefit.
Read more about Dr. Perou's work in The New York Times
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.