July 10, 2000
A Johns Hopkins research team has discovered a new family of genes that contributes to the process of malignancy, shedding new light on the abnormalities that give rise to the aggressive childhood cancer, Burkitt's lymphoma --as well as lymphoma, leukemia, prostate, ovarian, lung and breast cancer.
Scientists have long known that the "myc" family of genes plays a prominent role in tumor formation, also called neoplastic transformation. The Hopkins team, focusing on c-myc, found that another gene called the HMG-I/Y gene is a key genetic "target" necessary for Myc-mediated transformation.
"When we blocked expression of this target gene in Burkitt's lymphoma cell lines, the cancer cells revert back to normal-appearing cells. This could point the way to new therapies for one of the most aggressive childhood cancers, as well as other cancers associated with increases in the HMG-I/Y gene," says principal investigator Linda Resar, M.D., an assistant professor in the Division of Pediatric Hematology at Johns Hopkins University School of Medicine.
Increased expression of the c-myc gene has been previously linked to the development of Burkitt's lymphoma and several other cancers. In a study published in the August issue of Molecular and Cellular Biology, the Hopkins team showed in laboratory cell cultures that a protein made by c-myc binds to and directly stimulates HMG-I/Y. It is increased expression of HMG-I that causes normal cells to proliferate or grow like cancer cells.
The team then injected cells with increased HMG-I into mice and found they formed tumors. Conversely, blocking expression of HMG-I reversed abnormal growth. "Taken together, these findings suggest that HMG-I/Y genes may represent a new class of cancer-causing genes, or oncogenes," Resar says.
Characterized by rapidly growing abdominal tumors, Burkitt's lymphoma is one of the three major types of pediatric non-Hodgkin's lymphomas, representing 40 percent of that group. According to the American Cancer Society, approximately 57,000 children are diagnosed with non-Hodgkin's lymphoma per year in the United States, representing about six percent of cancers in children. While aggressive, Burkitt's lymphoma responds well to chemotherapy, and has a 90 percent survival rate if the tumor has not spread beyond the abdomen.