The investigators identified STAG2 as one of the most commonly mutated genes in bladder cancer, particularly in tumors that do not spread. The finding suggests that checking the status of the gene may help identify patients who might do unusually well following cancer treatment, says the study's senior investigator, cancer geneticist Todd Waldman, MD, PhD, a professor of oncology at Georgetown Lombardi.
"Most bladder cancers are superficial tumors that have not spread to other parts of the body, and can therefore be easily treated and cured. However, a small fraction of these superficial tumors will recur and metastasize even after treatment," he says.
Because clinicians have been unable to definitively identify those potentially lethal cancers, all bladder cancers patients — after surgery to remove tumors — must undergo frequent endoscopic examinations of their bladder to look for signs of recurrence, says Waldman. This procedure, called cystoscopy, can be uncomfortable and is expensive.
"Our data show that STAG2 is one of the earliest initiating gene mutations in 30-40 percent of superficial or 'papillary-type' bladder tumors, and that these tumors are unlikely to recur," says David Solomon, MD, PhD, a lead author on the study. Solomon is a graduate of the Georgetown MD/PhD program and is currently a pathology resident at the University of California, San Francisco.
"We have developed a simple test for pathologists to easily assess the STAG2 status of these tumors, and are currently performing a larger study to determine if this test should enter routine clinical use for predicting the likelihood that a superficial bladder cancer will recur," Solomon says.
For the study, the researchers examined 2,214 human tumors from virtually all sites of the human body for STAG2 inactivation and found that STAG2 was most commonly inactivated in bladder cancer, the fifth most common human cancer. In follow up work, they found that 36 percent of low risk bladder cancers — those that never invaded the bladder muscle or progressed — had mutated STAG2. That suggests that testing the STAG2 status of the cancer could help guide clinical care, Waldman says. "A positive STAG2 mutation could mean that patient is at lower risk of recurrence."
The researchers also found that 16 percent of the bladder cancers that did spread, or metastasize, had mutated STAG2.
STAG2 mutations have been found in a number of cancers, and this finding in bladder cancer adds new information, he says.
Contributing co-authors include researchers from the University of California, San Francisco; the University of Texas MD Anderson Cancer Center; Weill Cornell College of Medicine; the National Cancer Institute, the National Human Genome Research Institute; Johns Hopkins University School of Medicine; the University of Colorado Cancer Center; Hospital Kassel (Germany); University Hospital Ulm (Germany); Hospital Am Eichert (Germany); and Leiden University Medical Center (Netherlands).
This work was supported by National Institutes of Health grants (R01CA169345, R01CA159467, and R21CA143282), and the MD Anderson Cancer Center Bladder Cancer SPORE grant (P50CA091846).
A provisional patent application has been filed by Georgetown University for the technology described in this paper, on which Waldman, David A. Solomon, and Jung-Sik Kim are the inventors.
About Georgetown Lombardi Comprehensive Cancer Center
Georgetown Lombardi Comprehensive Cancer Center, part of Georgetown University Medical Center and MedStar Georgetown University Hospital, seeks to improve the diagnosis, treatment, and prevention of cancer through innovative basic and clinical research, patient care, community education and outreach, and the training of cancer specialists of the future. Georgetown Lombardi is one of only 41 comprehensive cancer centers in the nation, as designated by the National Cancer Institute (grant #P30 CA051008), and the only one in the Washington, DC area. For more information, go to http://lombardi.georgetown.edu.
About Georgetown University Medical Center
Georgetown University Medical Center is an internationally recognized academic medical center with a three-part mission of research, teaching and patient care (through MedStar Health). GUMC's mission is carried out with a strong emphasis on public service and a dedication to the Catholic, Jesuit principle of cura personalis – or "care of the whole person." The Medical Center includes the School of Medicine and the School of Nursing & Health Studies, both nationally ranked; Georgetown Lombardi Comprehensive Cancer Center, designated as a comprehensive cancer center by the National Cancer Institute; and the Biomedical Graduate Research Organization (BGRO), which accounts for the majority of externally funded research at GUMC including a Clinical and Translational Science Award from the National Institutes of Health.
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