Researchers from MIT’s Koch Institute for Integrative Cancer Research, the Broad Institute of MIT and Harvard, and the Dana-Farber Cancer Institute have published a study in Nature Biotechnology demonstrating that new experimental and analytical techniques for studying rare tumor cells in the bloodstream can provide a minimally invasive window into the genetics of metastatic prostate cancer. Bringing together oncologists, engineers, and computational biologists, the team describes proof-of-concept work demonstrating how to accurately map mutations in the DNA of rare circulating tumor cells (CTCs). The work sets the foundation for future comprehensive surveys of the genomics of CTCs applied to other cancer types and across large numbers of samples.
“From a pragmatic standpoint, having the resolution to identify individual point mutations in tumor DNA for which targeted therapies already exist or are in development is critical to be able to make decisions on which treatment may be best for an individual patient. The application of this process to samples from prostate cancer patients demonstrates that information about single-nucleotide variants in individual CTCs can be used to understand the genomics of the underlying cancer,” explains Koch Institute faculty member J. Christopher Love, PhD, co-senior author of this work.
The drop in the cost of genomic sequencing as well as advances in tools for amplifying the amount of genetic material of a single cell, i.e., making copies of its genome to sequence it comprehensively, have resulted in great advancements in technologies and approaches for sequencing single cells. However, the low number of CTCs in circulation and the noise associated with errors in the copy of the genetic material have historically made it difficult to sequence single-nucleotide variants in individual CTCs. The newly published study offers a set of experimental and analytical protocols to achieve the necessary level of sensitivity. Read the study abstract.
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