Who we are
The Center for Cancer Evolution (CCE) was founded in 2016 by Drs. Michor, Pellman, and Polyak at the Dana-Farber Cancer Institute.
The CCE focuses on understanding cancer evolution through a multi-disciplinary approach. Our goal is to understand the mechanisms behind tumor evolution, metastasis formation, emergence of drug resistance to ultimately provide more specialized and effective patient care in a variety of different cancer types.
In situ single-cell analysis identifies heterogeneity for PIK3CA mutation and HER2 amplification in HER2-positive breast cancer, Nature Genetics, 2015
Detection of minor, genetically distinct subpopulations within tumors is a key challenge in cancer genomics. Here we report STAR-FISH (specific-to-allele PCR-FISH), a novel method for the combined detection of single-nucleotide and copy number alterations in single cells in intact archived tissues. Using this method, we assessed the clinical impact of changes in the frequency and topology of PIK3CA mutation and HER2 (ERBB2) amplification within HER2-positive breast cancer during neoadjuvant therapy. We found that these two genetic events are not always present in the same cells. Chemotherapy selects for PIK3CA-mutant cells, a minor subpopulation in nearly all treatment-naive samples, and modulates genetic diversity within tumors. Treatment-associated changes in the spatial distribution of cellular genetic diversity correlated with poor long-term outcome following adjuvant therapy with trastuzumab. Our findings support the use of in situ single cell-based methods in cancer genomics and imply that chemotherapy before HER2-targeted therapy may promote treatment resistance.