The image depicts a brain giving rise to two trees, one healthy and one dying, to illustrate tumors that come from the same brain tissue can have vastly different prognoses. | Jae-June Lee
Computational biologist Roel Verhaak’s work on a new classification system for brain tumors that could improve the diagnosis and treatment of patients has earned him this year’s AAAS Martin and Rose Wachtel Cancer Research Award.
Examining the genomic profiles of more than 1,000 brain cancer patients, Verhaak and his colleagues at The Cancer Genome Atlas (TCGA) have identified new subtypes of the most common type of brain tumor, the glioma.
The subtypes shed light into the molecular basis of brain cancer and have been adopted by multiple clinical centers worldwide. The results from Verhaak and others also prompted the World Health Organization to revise its classification of tumors of the central nervous system earlier this year.
“Dr. Verhaak’s vital work advances the way we diagnose brain cancer,” said AAAS CEO Rush Holt, executive publisher of the Science family of journals. “In identifying genomic markers for the most common brain tumors, his innovation promises to improve patient treatment and outcomes, and brings the power of precision medicine to the forefront of cancer treatment.”
Verhaak, an associate professor at the University of Texas MD Anderson Cancer Center, was honored at an award ceremony at the U.S. National Institutes of Health on Friday, 5 August. He also wrote a Focus article on his research, which was published in Science Translational Medicine.
The annual AAAS Martin and Rose Wachtel Cancer Research Award, which includes a $25,000 prize, recognizes young cancer researchers who have made significant advances in the field of cancer. This year’s honorable mentions went to Nicola Aceto, an assistant professor from the University of Basel, and Eliezer Van Allen, an assistant professor at Dana-Farber Cancer Institute.
Roel Verhaak accepts cancer research award from Rush Holt, far right, as Yevgeniya Nusinovich, far left, and Tom Misteli, director of the Center for Cancer Research at the National Cancer Institute, look on during 5 August ceremony at the National Institutes of Health. | Jean Mendoza/AAAS
“Dr. Verhaak was selected for the Wachtel Award in recognition of his fundamental contributions to brain tumor genomics,” said Associate Editor of Science Translational Medicine Yevgeniya Nusinovich, who oversaw the award selection committee. “Although this work is relatively recent, the classification system pioneered by Dr. Verhaak and his colleagues is already internationally known and widely used by other researchers.”
Brain cancer patients are usually diagnosed using a biopsy, which can reveal tissue structures and other histological features that foretell cancer. However, visually examining a tissue under a microscope can be subjective, and the diagnosis often determines the course of patient treatment.
“If you give the same slide of the same tumor from the same patient to two pathologists, there’s only about 50% to 70% concordance between them,” said Verhaak. “The discordance can be substantial. This is especially true for the lower-grade cases.”
In search of a more objective approach, Verhaak and his team at TCGA crunched genomic sequencing data from 1,122 glioma patients. They identified genomic abnormalities or markers that revealed seven distinct subgroups of glioma, opening the door to a genome-based classification system.
“The good thing about these markers is you either have them or you don’t. There’s no subjectivity,” said Verhaak. “The whole field is moving to this direction … from histopathology to molecular markers.”
In particular, Verhaak and his colleagues found that glioma subtypes were characterized by different patterns of a DNA process that alters how genes are expressed without changing their actual sequence. When the process, known as methylation, is combined with other clinical features, DNA methylation can strongly predict patients’ outcomes.
Clinical centers across the U.S., Canada, and Germany have begun to test for patients’ DNA methylation profiles, integrating molecular data and histology into their diagnostic process. A more accurate diagnosis, in turn, can guide personalized treatment strategies for glioma patients.
“The classification provides a basis that gives you a very strong idea about the prognosis of the patient and thereby, how hard you might want to try and hit the tumor,” said Verhaak. “For a patient with a poor prognosis, you may want to go full blast with chemotherapy and radiation. [For] a patient with a better prognosis, you may want to spare them from brain radiation.”
Efforts are currently underway to develop new and more targeted therapies for brain cancer. The new classification system could identify patients with specific subtypes of glioma who might benefit from a given drug.
“We do research because we think it’s important, not because we want to achieve awards. But it’s really humbling and awesome to be recognized in that way,” said Verhaak. “I’m getting the award as recognition of my lab, not just myself.”
Associated image: A microscopic image of an aggressive malignant brain tumor, known as anaplastic astrocytoma. | Wikimedia/ CC BY-SA 3.0 US