Individualizing Cancer through Mutations

Rebecca Moragne, TuftScope Research-Highlights Editor

Today, brain tumors are measured by location, if they have metastasized, and how they visually appear under a microscope. But what if instead they were evaluated by the type of mutations that initiated their development in the first place? Robert Jenkins, M.D., Ph.D., at Mayo Clinic and Margaret Wrensch, M.P.H., Ph.D., at the University of California, San Francisco, are exploring the genetic components of glioma brain tumors to develop a test for brain cancer prognosis and treatment.

            Gliomas are the most common type of brain tumor and are broken in to three types: astrocytomas, oligodendrogliomas, and oligoastrocytomas (a mixture of the first two). Basing a brain tumor solely off of its name may fail to acknowledge many individual characteristics of a tumor. “It is like walking onto a used car lot and trying to figure out how fast a car will drive or how reliable its brakes are by looks alone. One sports car might move faster than another, and a perfectly nice-looking sedan might have perfectly shoddy brakes. The only way to know for sure is to take a look under the hood.” To further individualize each glioma, Jenkins and Wrensch are analyzing the mutations in gliomas.

            All cancers begin with a mutation: some are recently developed while others have existed since utero. Jenkins and Wrensch are focusing on the gene mutations 1p/19q co-deletion, the IDH mutation, and the TERT mutation. Most gliomas either have all three mutations, the IDH and TERT mutation, only the IDH mutation, only the TERT mutation, or none of the three mutations. And the gliomas within each of the five mutation categories have similar characteristics including age of onset and age of survival. Knowing these characteristics from a genetic analysis is no small discovery. Gaining a better understanding of a glioma can help with treatment, specifically therapies that target the unique mutation. 

 

Jenkins and Wrensch are now beginning to apply their research in a clinical setting. They are using “gene chip” technology to locate mutations in a tumor. These mutations appear as duplicated or missing DNA segments. And patient outcomes from treatment with knowing this additional information are superior than those without it because the mutation knowledge aids in knowing how a specific glioma will respond to a treatment and which treatment is best. No two patients are alike and neither are two gliomas. Sometimes the treatment is not worth the outcome and many times it is, but allowing a patient to have a better understanding of his or her prognosis is extremely valuable.

            Going forward, Jenkins wants to expand his exploration on cancer genetics and mutations. His laboratory is using CRISPR, a genome-editing tool, to cause the glioma mutations in cells in order to observe how the cancer develops. Jenkins states, “It is possible that these tumors have been around since the person was born…It may very well have started in utero, and it just takes 30 years for them to come to clinical attention. Or the vulnerable period may be much later, but frankly we’ll never know until we do the experiments.” By specializing the treatment and therapy for each individual cancer, Jenkins and Wrensch are ultimately one step closer to identifying the cure for the disease.

 

Broadfoot, M. V. (2016). Guest post: Battling brain cancers through genomics. National Brain Tumor Society. Retrieved from http://blog.braintumor.org/guest-post-battling-brain-cancers-through-genomics/