PHILADELPHIA—The international hunt to find more genetic risk markers for testicular cancer is expanding. A team of researchers led by Katherine L. Nathanson, MD, deputy director of the Abramson Cancer Center and the Pearl Basser Professor for BRCA-Related Research in the Perelman School of Medicine at the University of Pennsylvania, was recently awarded $5.4 million over five years from the National Institutes of Health to continue the long-standing genomics work of the TEsticular CAncer Consortium (TECAC).
A total of nearly $7 million has been awarded to TECAC, which includes researchers from 27 institutions around the world, whose collaborative goal is understand the genetic susceptibility to testicular germ cell tumors (TGCT).
TGCT are the most common cancer in the United States and Europe in men between the ages of 15 to 45, and the number of cases has continued to rise over the past 40 years. Approximately 50 percent of the risk of disease is due to genetic factors, higher than for other cancer types.
To date, TECAC has identified 22 novel susceptibility alleles, bringing the total number of risk markers to 66. Nathanson led a study in 2017 published in Nature Genetics that identified eight of those markers in previously unknown gene regions, as well as four in previously identified regions.
Members of TECAC also were the first to identify CHEK2, a moderate penetrance gene for TGCT. Penetrance refers to the proportion of people with a mutation in specific gene. Unlike other solid tumor types (e.g. breast, ovarian), the inherited risk of TGCT is likely due to multiple variants rather than any single gene.
“Our work has revealed critical roles for genetic variants and mutations in testicular germ cell tumors and defined the biology of TGCTs as associated with defects in maturation of male germ cells, but there’s still much more to discover with this highly heritable disease,” Nathanson said. “This grant will allow us to continue to pool our resources and expertise to better understand its biology and etiology, as well as provide data that can help identify men at higher risk of the disease and in need of surveillance.”
The latest round of funding will focus on three projects: identify rare and common variants using whole exome genetic sequencing from biosamples of more than 2,000 men; conduct a transcriptome-wide association study, or TWAS, to identify novel candidate susceptibility genes in nearly 250,000 men (the largest to date); and further evaluate any variants or gene discovered from those two projects using tools, such as CRISPR, in cells.
Other Penn collaborators on this grant (R01 CA164947 A1) include David Vaughn, Linda Jacobs, Li-San Wang and Mingyao Li.
Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation’s first medical school) and the University of Pennsylvania Health System, which together form a $8.6 billion enterprise.
The Perelman School of Medicine has been ranked among the top medical schools in the United States for more than 20 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $494 million awarded in the 2019 fiscal year.
The University of Pennsylvania Health System’s patient care facilities include: the Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center—which are recognized as one of the nation’s top “Honor Roll” hospitals by U.S. News & World Report—Chester County Hospital; Lancaster General Health; Penn Medicine Princeton Health; and Pennsylvania Hospital, the nation’s first hospital, founded in 1751. Additional facilities and enterprises include Good Shepherd Penn Partners, Penn Medicine at Home, Lancaster Behavioral Health Hospital, and Princeton House Behavioral Health, among others.
Penn Medicine is powered by a talented and dedicated workforce of more than 43,900 people. The organization also has alliances with top community health systems across both Southeastern Pennsylvania and Southern New Jersey, creating more options for patients no matter where they live.
Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2019, Penn Medicine provided more than $583 million to benefit our community.