Whole genome sequencing: Personalized medicine’s next step

Carlo Bifulco, M.D.

Carlo Bifulco, M.D.
Pathologist, Providence Pathology and Diagnostic Laboratories

Published May 2013

Medicine is undergoing a major shift toward personalized health care, a model in which preventive and therapeutic practices are custom designed for each patient’s specific needs.

For cancer, personalized treatment is made possible by rapid and dramatic advances in DNA sequencing, which enables us to decode tumor genomes, and by new drugs that selectively target damaged or mutated genes. These developments allow us to match drugs to specific tumors, resulting in better outcomes, less toxicity and lower costs.

Providence Pathology and Diagnostic Laboratories already plays an important role in detecting tumor-driver mutations and tumor pathways that will respond well to certain drugs. It performs or coordinates tests for several molecular targets in multiple tumor types, including breast, colon, lung and hematologic malignancies. Test results are routinely incorporated into diagnostic pathology reports.

Now we’re preparing for the next leap forward in personalized care. We’re transitioning from single gene mutation testing – that is, focusing on one gene at a time for specific targetable mutations – to mapping and decoding whole genomes. By comparing the patient’s normal DNA to the tumor DNA, we can identify all the potentially “actionable” mutations. This allows for more targeted, personalized treatment.

A multiphase approach
At Providence Cancer Center, this process will be developed in stages. First we’ll focus on characterizing cancers through next-generation sequencing of gene groups currently associated with specific tumor types. Later as the technology and data interpretation become standardized and increasingly robust, we’ll extend this approach to the whole exome (the part of the genome most frequently altered in tumor-driving mutations). The ultimate goal is to complete genetic profiling of tumors with the sequencing of whole tumor genomes.

This shift in cancer diagnostics and treatment is not an easy task, but in the long run, this new approach will result in better and more affordable diagnostics and, most importantly, in improved clinical outcomes.

Lastly, there is strong evidence that cancer outcomes are driven not only by tumor biology, but also by the immune system’s ability to keep the tumor in check. Providence Cancer Center is an international leader in developing and adopting therapies that use the body’s immune system to fight cancer.

Current protocols based on ipilimumab and interleukin-2, as well as on novel agents such as anti-OX-40 and vaccine-based therapeutics, are just some of Providence Cancer Center’s achievements. Because there is an important role for personalized immunologic therapy, our labs are developing tests to characterize a patient’s immune response to a tumor. We’re hopeful that this immunoprofiling approach will allow for further personalized use of immunotherapeutic agents in cancer treatment.