The research began at Dana-Farber Cancer Institute in Boston and continued at MD Anderson after Ronald DePinho, M.D., became president in September 2011.Working with cell lines of glioblastoma multiforme, the most lethal type of brain tumor, investigators looked at passenger deletions ― genes co-deleted along with tumor-suppressor genes, but not directly involved in cancer promotion.
They wiped out glioblastoma cells that had deletions of the metabolic gene ENO1 on both copies of chromosome one when they also inhibited the function of ENO2 on chromosome seven. Both genes encode for an enzyme crucial to glycolysis, the processing of glucose into energy that is particularly important to solid tumors. Cells can tolerate the loss of ENO1 or ENO2, but not both. Although ENO1 deletions occur in a small subset of glioblastoma patients, passenger deletions are frequent in the cancer genome and occur in most cancer types, note the investigators.
“Passenger deletions occur in hundreds of genes in many types of cancer,” says DePinho, senior author of the paper. “Our model for glioblastoma multiforme should apply to developing personalized treatments for other cancers as well.”
Funding was from the National Cancer Institute, the American Cancer Society and the Howard Hughes Medical Institute, as well as a Harvard PRISE fellowship, the Dana-Farber Cancer Center/Harvard Cancer Center Myeloma SPORE (Specialized Programs of Research Excellence) grant and the Ben and Catherine Ivy Foundation.