Molecular composition of multiple tumors shows genomic differences
Cleveland, OH & Buffalo, NY — While the majority of prostate cancers are slow growing and not fatal, some are aggressive and lethal. That fact underscores both the importance of new evidence that prostate tumors can be genetically different in individual patients and the implications of these research findings for patients and oncologists.
Genomic fingerprinting has helped physicians to predict the aggressiveness of an individual’s cancer based on the tumor’s genetic makeup and to tailor their treatment plans accordingly. However, in the majority of cases, while there are multiple prostate tumors present, typically only the largest tumor is fingerprinted. Writing in the journal European Urology, a research team led by Hannelore Heemers, Ph.D., of Cleveland Clinic’s Lerner Research Institute Department of Cancer Biology and Song Liu, PhD, Vice Chair of Bioinformatics at Roswell Park Comprehensive Cancer Center in Buffalo, has demonstrated that when genomic fingerprinting is performed on only a single tumor sample, a smaller but more aggressive tumor could potentially be missed.
For the study, “Intratumoral and Intertumoral Genomic Heterogeneity of Multifocal Localized Prostate Cancer Impacts Molecular Classifications and Genomic Prognosticators,” the team used next-generation sequencing techniques to genotype prostate tumors from four men who underwent radical prostatectomy. They also examined public data from the Cancer Genome Atlas to confirm their findings.
“We examined the molecular composition of heterogeneous cancerous tumors in a patient’s prostate. We found a lot of genetic differences among these tumors, and concluded that information from a single cancer biopsy is not sufficient to guide treatment decisions,” said Dr. Heemers. “Precise treatment is more complicated and the findings demonstrate a weakness in current genetic fingerprinting in prostate cancer.”
“High risk prostate cancers differ genetically among patients, among the different tumors within an individual patient and even within different sections of a single tumor,” said James Mohler, MD, Chair of the Department of Urology at Roswell Park Comprehensive Cancer Center, member of the investigative team and co-author. “Clinicians need to be careful about using the information from a gene-based test, because the analysis may not have been performed on the most aggressive portion of a man’s prostate cancer.”
In “Disrupting the Status Quo in Prostate Cancer Diagnosis,” an editorial published in the same journal, Alastair David Lamb, MB.ChB., Ph.D., of Cambridge University Hospitals, and co-authors write: “Several aspects of this study are impressive. [The authors] addressed an important clinical and molecular question: What effect does tumor heterogeneity have on decision making in prostate cancer, specifically, with respect to molecular taxonomies of the disease?”
The study authors note that the use of genomic analysis to personalize treatment plans is in its infancy and that many more large studies will be required to develop next-generation prognostic tools that can be relied on to guide treatment selection and planning for men with prostate cancer.
Editor’s Note: Relevant Broll available upon request.
About Cleveland Clinic Lerner Research Institute
The Lerner Research Institute (LRI) is home to Cleveland Clinic’s laboratory, translational and clinical research. Its mission is to promote human health by investigating in the laboratory and the clinic the causes of disease and discovering novel approaches to prevention and treatments; to train the next generation of biomedical researchers; and to foster productive collaborations with those providing clinical care. In 2015, LRI researchers published nearly 600 articles in high-impact biomedical journals (top 10% of all biomedical journals). LRI’s total annual research expenditure was $251 million in 2015 (with $104 million in competitive federal funding). Approximately 1,200 people (including approximately 150 principal investigators, 200 research fellows, and about 100 graduate students) in 12 departments work in research programs focusing on cardiovascular, cancer, neurologic, musculoskeletal, allergic and immunologic, eye, metabolic, and infectious diseases. The LRI has more than 700,000 square feet of lab, office, and scientific core services space. LRI faculty oversee the curriculum and teach students enrolled in the Cleveland Clinic Lerner College of Medicine (CCLCM) of Case Western Reserve University – training the next generation of physician-scientists. Institute faculty also participate in multiple doctoral programs, including the Molecular Medicine PhD Program, which integrates traditional graduate training with an emphasis on human diseases. The LRI is a significant source of commercial property, generating 54 invention disclosures, 14 licenses, and 76 patents in 2015.
About Roswell Park Comprehensive Cancer Center
The mission of Roswell Park Comprehensive Cancer Center is to understand, prevent and cure cancer. Founded in 1898, Roswell Park is one of the first cancer centers in the country to be named a National Cancer Institute-designated comprehensive cancer center and remains the only facility with this designation in Upstate New York. The Institute is a member of the prestigious National Comprehensive Cancer Network, an alliance of the nation’s leading cancer centers; maintains affiliate sites; and is a partner in national and international collaborative programs. For more information, visit www.roswellpark.org, call 1-800-ROSWELL (1-800-767-9355) or email AskRoswell@Roswellpark.org. Follow Roswell Park on Facebook and Twitter.
Deb Pettibone, Public Information Specialist