Researchers have discovered that whole-genome sequencing—rather than the current standard of exome sequencing—may allow physicians to better identify genetic changes that drive cancer development and growth, and create the most effective, personalized treatment plans for patients with classical Hodgkin lymphoma, according to a novel study published by Maura et al in Blood Cancer Discovery.
Background
While exome sequencing—which reads only protein-coding genes—has been extremely fruitful at detecting some specific point mutations and other variants that propel cancer development, it paints an incomplete picture. Mutations in noncoding genomic regions can also govern gene expression.
However, researchers have found that whole-genome sequencing can read virtually all of the mutations in both protein-coding and noncoding regions of the genome and can detect other changes that may initiate cancer development. In addition, this type of sequencing may be capable of identifying a wide range of structural variations—including chromothripsis.
“We found many genomic events that had never been recorded before. It’s the best technology we’ve found to identify new cancer drivers,” explained study coauthor Craig H. Moskowitz, MD, Professor of Medicine and Physician-in-Chief of the Oncology Service Line at the Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine.
Study Methods and Results
In the new proof-of-concept study, the researchers used whole-genome sequencing to identify many structural variations in classical Hodgkin lymphoma as well as mutational signatures associated with chemotherapy. In addition, whole-genome sequencing provided temporal insights into how the tumors evolved. Reconstructing tumor chronology could play a major role in treatment selection.
“It’s important to know how a tumor developed over time,” emphasized first study author Francesco Maura, MD, Assistant Professor of Medicine and Co-Leader of the Myeloma Genomic Lab at the Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine. “We need to know which mutations were acquired and in what order. If we prescribe a targeted therapy, we want it to target genomic alterations that are shared throughout the tumor, rather than the subclones that came later and are relatively rare,” he added.
The researchers were able to isolate and examine the rare Hodgkin and Reed Sternberg cells found in classical Hodgkin lymphoma. They highlighted that this approach, combined with whole-genome sequencing, could provide many new insights into classical Hodgkin lymphoma and other cancers.
“Cancers are incredibly complex diseases, and we still have a long way to go before we fully understand them,” underscored study coauthor C. Ola Landgren, MD, PhD, Professor of Medicine, Director of the Myeloma Research Institute, and Co-Leader of the Translational and Clinical Oncology Research program at the Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine. “By leveraging [whole-genome sequencing], we can better assess tumor evolution, identify structural issues, and hopefully gain new therapeutic insights,” he concluded.
Disclosure: The research in this study was supported by the Children’s Oncology Group, the Hartwell Foundation, the Gant Family Foundation, the Sylvester Comprehensive Cancer Center National Cancer Institute (NCI) Core Grant, and the Memorial Sloan Kettering Cancer Center NCI Core Grant. The researchers were additionally supported by the American Society of Hematology, the Riney Family Foundation, the National Institutes of Health, the Gant Family Foundation, and The Hartwell Foundation. For full disclosures of the study authors, visit aacrjournals.org.
