The science underlying Foundation Medicine had its roots in a 2007 paper published by Levi Garraway and Matthew Meyerson, cancer researchers at the Broad Institute, in Cambridge, Massachusetts.
They came up with a speedy way to find 238 DNA mutations then known to make cells cancerous. At the time, DNA sequencing was still too expensive for a consumer test, but their strategy was to allow screening for a reasonable cost.”
Garraway’s team, which included first authors Roman Thomas, Alissa Baker, and Ralph DeBiasi, and a collaboration with Matthew Meyerson, HMS associate professor of pathology at DFCI, created assays for 238 known mutations found in 17 human oncogenes. The DNA from 1,000 tumor samples collected at a variety of institutions was analyzed for mutations using mass spectrometry, which can detect point mutations in small pieces of DNA using the predicted mass corresponding to the bases examined. Advantages of the method include its low cost and sensitivity—it can detect a variant base present in the sample at a level of 10 percent or less. Garraway said that sensitivity is important since many tumor samples contain a heterogeneous mix of tissue, only part of which may be cancerous.
Garraway said his next step is to create a version that includes more than a thousand assays for mutations in 90 different genes. The cost of the technology—less than $100 per sample in this analysis, but more for a more comprehensive scan—is within reason for clinical use. Part of the challenge of making this technique widely usable, however, is developing software to collect and analyze data from the assays. Currently, the technique can look only for mutations that switch on oncogenes, not those that turn off tumor suppressors; the first approach is more manageable since fewer ways exist to switch genes on than to turn them off. The method also misses other genomic events, like amplifications and deletions of DNA. But Garraway hopes that the basic concept can be tweaked to make it possible to study efficiently a range of genomic events in cancer.