Cold Spring Harbor Laboratory
Cold Spring Harbor, New York
Tumors are composed of a complex mixture of cells with different genomic makeups that influence response to treatment and tumor behavior. Technology developed by Dr. Wigler in collaboration with BCRF grantee James Hicks at Cold Spring Harbor Laboratory makes it possible to study the complexity of breast cancer at the single cell level and to begin developing new diagnostic tools that will aid in therapeutic management of the disease. These methods that involve single cell genomic sequencing provide a new approach to understanding the lineage of a cancer cell and the incredible genomic flexibility that allows cancer cells to change rapidly in response to treatment. Dr. Wigler and colleagues are now studying ways to use single cell sequencing to answer important questions in breast cancer research, such as: Why do some tumors metastasize and others do not? Which cells are capable of leaving the primary site? And if they leave, where do they go? This exciting new technology has the potential to revolutionize our thinking about cancer growth and opens up immense new clinical possibilities, such as improvements in the assessment of prognosis and treatment, evaluation of cancer risk, and early detection of breast cancer or breast cancer recurrence.
Cold Spring Harbor Laboratory scientist Michael Wigler, PhD, in collaboration with James Hicks, PhD, is analyzing the genomes of women with breast cancer in research aimed at eliminating "trial-and-error" approaches to therapy. This work is leading to diagnostic tests capable of distinguishing cancers likely to spread and should receive aggressive treatment from those that are benign and can be left untreated. In this effort, Drs. Wigler and Hicks are using powerful technologies that they developed to analyze genomic and epigenetic changes in thousands of breast cancers and have identified three distinct categories of breast cancer DNA profiles associated with different outcomes for patients. Their research has provided important information about which patients are most likely to benefit from treatment with specific drugs, such as taxol and Herceptin®. Drs. Wigler and Hicks have also developed a sensitive technology called single nucleus sequencing (SNS) that can identify genetic changes in very small samples, which can be used to follow genetic changes as tumors progress and to identify specific changes that can predict which tumors are likely to metastasize. The group is continuing to make technological improvements to make it affordable and feasible for SNS to be used as a monitoring tool for early detection of cancer cells in the blood, and to direct therapy based on the genetic makeup of those circulating cancer cells.