Multidisciplinary Team Brings Integrated, Genomics Approach to Brain Cancer
Whole genome sequencing techniques are commonly used in research, but are not a routine part of clinical care. A collaborative effort by investigators from BWH, Dana-Farber Cancer Institute and Boston Children’s Hospital has shown that the genomic profiling techniques researchers typically use to examine a patient’s DNA could also have a place in the clinic.
Earlier this year, Keith Ligon, MD, PhD, Azra Ligon, PhD, Brian Alexander, MD, MPH, and Rameen Beroukhim, MD, PhD, along with other researchers from BWH’s departments of Pathology, Neurosurgery and Radiation Oncology; Dana-Farber’s departments of Medical Oncology and Radiation Oncology; and from Boston Children’s Hospital Department of Pathology published a paper featured in Neuro-Oncology describing this approach.
The team’s research puts to the test two techniques that look across the whole genome of brain tumors: OncoCopy, used to detect gene deletions and duplications, and OncoMap, used to detect specific mutations.
OncoCopy is a high resolution test run in the BWH Clinical Cytogenetics Division that’s used to identify missing or extra copies of genes within the tumor’s DNA. The test is a specific and sensitive one that allows for the causes of cancer to be discovered.
OncoMap is a test run in the BWH Molecular Pathology Division that looks at specific sites in a tumor’s DNA to identify if a single “letter” in the DNA code is mutated. It gives yes or no answers for a set number of sites. OncoMap was the first such test used at the Dana-Farber/Brigham and Women’s Cancer Center to genotype patients for the first one and a half years of the program. Following the success of the first test, Ligon says the program has now moved on to using a new generation of sequencing called OncoPanel that tests more than 300 cancer causing genes for defects.
In order to use these tools in a clinical setting, extensive collaboration of the team of doctors needs to happen up front. Traditionally, pathologists look at brain cancer cells under a microscope to characterize and distinguish them. Yet, brain tumor differences are also found at a deeper level. To see these differences, Ligon and his pathology colleagues must coordinate with BWH neurosurgeons.
The coordination, like a relay race, involves several strategic handoffs. Before surgery, neurosurgeons and pathologists discuss the size of the brain tumor and think through how much tissue – living and dead – needs to be extracted. After surgery, the neurosurgeon shares a sample of living tissue (only living tissue is effective for testing) with the pathologist. Next the pathologist slides the samples under a microscope to consider the structure and physical abnormalities. It’s handed off to another researcher specialized in immunocytochemistry testing to identify unique antigens, or cellular proteins, that distinguish one cancer from another. Finally, the tumor’s genome is tested and sequenced using OncoCopy, OncoMap or OncoPanel for multiple colleagues on the team to analyze. The results are then able to be used by surgeons, oncologists and radiation oncologists to determine the best course of treatment and the prognosis of the patient.
“It’s this process that helps us understand the unique genetic components of a patient’s brain tumor that can lead to personalized and more effective treatments for brain tumors and other cancers,” Ligon said. “The new and more accurate information gained is the very essence of ‘Precision Medicine’ and is hoped to lead to better therapies for every patient.”