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 to 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 cmyc, found that another gene called the HMGI/Y gene is a key genetic "target" necessary for myc-mediated transformation.
"When we block 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 HMGI/Y gene," says principal investigator Linda Resar, an assistant professor in the Division of Pediatric Hematology at the School of Medicine.
Increased expression of the cmyc 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 cmyc binds to and directly stimulates HMGI/Y. It is increased expression of HMGI that causes normal cells to proliferate or grow like cancer cells.
The team then injected cells with increased HMGI into mice and found they formed tumors. Conversely, blocking expression of HMGI reversed abnormal growth. "Taken together, these findings suggest that HMGI/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 6 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.