A single gene separates aggressive and non-aggressive lymphatic system cancer

Thymoma is a cancer derived from the epithelial cells of the thymus, an organ critical to the lymphatic system where T-cells, or so-called “killer cells,” mature. Very little is known about the role of the gene mutation GTF2l in human tumors, but scientists from Georgetown Lombardi Comprehensive Cancer Center and the National Cancer Institute say almost all indolent (slow growing and non-aggressive) forms of thymoma they tested have the mutation. They report their finding in the ?? issue of Nature Genetics.

“Indolent thymomas seldom become aggressive, so the discovery that a single gene can identify tumors that do not need aggressive care is an important development for our patients,” says the study's senior investigator, Giuseppe Giaccone, MD, PhD, associate director for clinical research at Georgetown Lombardi.

In addition to the clinical implications, the study is important because “it is highly unusual to find a single mutated gene that can define a class of tumors,” he said. “Usually a substantial number of genes are involved. In fact, we also found that the more aggressive thymomas express well-known cancer genes found in other tumors — which might give us clues about novel treatment of these cancers.”

The thymus is located in the chest behind the breastbone. Thymoma and a second type of cancer of the thymus called thymic carcinoma are rare. According to the National Cancer Institute, these cancers counted together make up for only .2 to 1.5 percent of all cancers— one case occurs in about every 700,000 individuals.

Most of the diagnosed patients have surgery, but, depending on the presumed aggressiveness of the cancer, some patients will have radiation and/or chemotherapy in addition or instead of surgery. “The use of these treatments in thymomas is controversial, because we know some patients don't need aggressive therapy, but until now, there's not been a clear way to know who those patients are,” Giaccone says.

Co-authors include: In-Kyu Kim, Kang-Seo Park, Sivanesan Dakshanamurthy and Yisong Wang from Georgetown Lombardi Comprehensive Cancer Center; Iacopo Petrini, Paul S Meltzer, James Gao, Robert L. Walker, Marbin Pineda, Yuelin J Zhu, Christopher Lau, Keith J. Killian, Sven Bilke, Donna Voeller and Jaime Rodriguez-Canales from the National Cancer Institute; Marco Lucchi and Gabriella Fontanini from Pisa University Hospital, Pisa, Italy; Paolo A Zucali from Humanitas Clinical and Research Center, Milan, Italy; and Fiorella Calabrese, Adolfo Favaretto and Federico Rea from Padua University Hospital, Padua, Italy.

The study was supported by the National Cancer Institute intramural research program and Georgetown Lombardi Comprehensive Cancer Center. The National Cancer Institute has filed a patent application on the technology described in this paper. Giaccone, Wang and Petrini are inventors on the patent.

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.