There is a commonly shared maxim in oncology: “The tissue is the issue.”
For decades, examining a biopsy under the microscope is where the diagnosis of a brain tumor began … and ended. However – since different tumors often appear to be alike under the microscope – the precise diagnosis was often questionable, leaving doctors and patients unsettled.
Today’s current approach goes much further thanks to molecular testing. Molecular testing checks for certain genes, proteins and other molecules in a sample of tissue and detects changes in genes and chromosomes that may cause or affect a specific disease such as cancer.
After surgery, each patient treated at the Gerald J. Glasser Brain Tumor Center has his/her tumor tissue sent for detailed molecular screening. Using targeted next-generation sequencing, the tumor is tested for mutations and rearrangements involving 219 genes associated with tumors of the central nervous system. The results of the molecular testing provide information about the tumor’s history, how aggressive it may behave and how it may respond to therapy. They may also provide targets for further treatment.
While technical, these examples show the importance of molecular testing:
- Consider the IDH (Isocitrate Dehydrogenase) gene. A mutated IDH result in a patient with glioblastoma indicates this tumor is a secondary glioblastoma that arose from a lower-grade tumor over time. Conversely, a “wild type” (non-mutated) IDH indicates the tumor began as a glioblastoma with a less promising overall prognosis. This distinction is critically important because of the implication it has on tumor behavior and overall prognosis.
- For patients on alkylating chemotherapies – the oldest type of chemo that damages the DNA of cancer cells to keep them from making more copies of themselves – knowing the difference between MGMT (Methylguanine-DNA Methyltransferase) methylated and unmethylated tumors can shed light on how the tumor will respond to treatment. MGMT methylated tumor cells have less of an ability to “undo” the damage caused by alkylating chemotherapies and therefore respond better to these treatments.
New treatments for brain tumors are being proposed every year. A common approach in developing new treatments is to use a drug that targets a specific mutation found in a subset of tumors. Each patient’s personalized molecular report helps determine which of these potential cutting-edge therapies may generate positive outcomes.
Since the typical molecular report is comprehensive, mutations that do not yet have treatments may be seen. This intelligence is critically important as future studies may tell us more about the mutation’s significance, and new drugs that focus on that mutation may become available.
Molecular reports drive our understanding of tumor behavior and treatment. They enable us to treat each individual patient’s signs and symptoms using their molecular results as a guide.