Last week I had the great privilege to join over 60 cancer investigators and bioinformaticians at the Cancer Genome Sequencing Summit, in Boston, MA.  Leading practitioners from major pharma and biotech companies were in attendance to discuss real opportunities to translate actionable information from foundational cancer genome research into effective clinical therapies.  I had extensive conversations with nearly half of them, and can say that we made more quality contacts for our company at this meeting than at any other event this year.

So, what's new in genomic analysis for cancer?   Interest in analysis software has moved beyond identification of basic germline variation to the genomic characterization of subclones and their evolution.   Variant callers must now support discovery of driver mutations in tumor / normal pairs and selection of patients for stratified clinical trials.   I see this as an opportunity for the commercial-grade RTG Investigator, with its fast, sensitive sequence search and accurate Bayesian variant caller,  to evolve into a compelling alternative for detection of somatic mutations in cancer research. 

At last month’s TCGA (The Cancer Genome Atlas) Scientific Symposium, open source tools for somatic calling were reviewed by Andrey Sivachenko of the Broad Institute.  In this video clip from the symposium, Sivachenko shows early evidence that an investigator benefits from overlapping the results from multiple callers.  The NIH-funded TCGA program has released data for more than 4,000 cases of human cancer so far, and promises to be a definitive resource for cancer investigation.  Links to TCGA Symposium video and slides can be found here.

The Cancer Genome Sequencing summit offered insight into the actual impact of this core research on potential therapies.  The first day agenda featured a number of presentations on the subject of driver mutations in cancer, including insightful talks from Dr Theresa Zhang (Merck) and Dr Koustubh Ranade (Medimmune).   It's critical that drivers (signal) be separated from the passengers (noise) so that the researcher can clearly identify, for any given tumor type, the relevant oncogenes and potential tumor suppressors.  Yet, somatic mutations are extremely rare, on the order of 1 in a million, compared to 1 in a thousand for germline variants and 1 in 100 for modern sequencing instrument error rates.  One will need to compare variant calls from alignment files of one or more tumors to that of the matched normal tissue to get a clear signal for potential path of investigation.

The second day agenda highlighted the application of patient stratification by large pharmaceutical companies to clinical trials of tailored therapies.  Particularly relevant talks were given by Mao Mao (Pfizer) and Kavitha Venkatesan (Novartis).  A drug or combination of drugs may be highly effective against a particular tumor, but only within a limited patient sub-population.  Thus, patient selection will be critical to the success of these trials.   Bio-markers must now be identified that uniquely define a set of patients for a trial of a particular tailored therapy.  There is a critical need to assess variants across a cohort of a specific phenotype that matches well to the patient population.  Variants must be called accurately across the cohort, not just with each person against the reference.

Real Time Genomics has invested in unique solutions for read mapping and variant calling that will support these requirements for genomic analysis in cancer research.  Through Early Access Program (EAP) relationships, we partner with aggressive research organizations to enable novel research opportunities.  Past EAP projects have resulted in variant detection with Complete Genomics data (VIB) and high throughput metagenomics with Illumina data (The Genome Institute at WUSTL). 

We are keen to partner now with pharmaceutical and biotechnology companies on genomic analysis methods that accelerate real world application of cancer therapies and cures.  Contact RTG today to seize the opportunity.  RTG Investigator sequence analysis software is available for free download for individual use, or for evaluation with large scale datasets by request.