Sep 29, 2011

Foundation Medicine grabs for the low-hanging fruit of NGS cancer diagnostics

I was at the CHI APPLYING NEXT-GENERATION SEQUENCING conference in Providence RI, where I heard an extremely interesting presentation from a new Genomics company called Foundation Medicine. This company plans to offer a clinical diagnostic test based on very deep sequencing of all exons from about 300 cancer related genes. They will sequence directly from pathologist's FFPE blocks using Illumina HiSeq to a depth of 500 to 1000X.

Here is a recent poster they presented at ASCO, but the information at the CHI conference was updated and more in depth.
ASCO poster

Here is why I think this is very important. First, this test will include all existing genes that are currently being tested for any type of cancer (BRCA1&2, KRAS, BRAF, HER2, EGFR, etc), but will include all exons and greater diagnostic sensitivity for mutations present in low abundance in heterogenous samples which may suffer from mixed tumor and normal tissue, multiple clones, mixed aneuploidy etc. It will likely also contain the majority of known pharmacogenomic genes. So this one test could put all the other providers of cancer related genetic tests out of business.

It is also very important that the test is highly targeted only at "actionable" genes. Foundation Med. plans to deliver a report for each patient (in 14 days) that lists all mutations observed in the diagnostic genes, as well as some key items drawn from the literature, clinical trials, and a curated knowledge base about treatments relevant to those genes. In the presentation, COO Kevin Krenitsky said that they typically found 2-3 mutated genes per patient. This is an amount of data that the oncologist or pathologist can reasonably be expected to deal with — rather than the hundreds to thousands of mutated genes with questionable to zero clinical implications that will be produced by whole genome sequencing.

Another interesting discovery reported by Foundation Med. was that in a small number of cases (perhaps 5%), they found mutations for genes that were associated with a different type of cancer. This suggests the use of a non-traditional drug, possibly in combination with other more typical therapies, as an individualized treatment for that one patient. There are currently about 30 drugs for which genetic information can aid in treatment decisions, but this is clearly an area of intense development. Foundation Med. can easily modify its test to include any relevant new genes. We are clearly heading to the point where every cancer patient will benefit from an individualized genomics workup.