Study identifies new tumor suppressor gene in Li-Fraumeni syndrome

In 1990 a research team based at the Massachusetts General Hospital (MGH) discovered the gene responsible for most cases of Li-Fraumeni syndrome, a rare inherited condition that leads to the frequent occurrence of several types of cancer in affected families. That gene - p53 - subsequently has proven to be one of the most important genes involved in the development of human cancer. In addition to the gene's role in Li-Fraumeni, non-inherited mutations to p53 are found in half of all human tumors.

Now a team based in the same MGH research lab has identified another gene that is mutated in some families that, without having p53 mutations, appear to have Li-Fraumeni or a closely related syndrome. Like p53 the new gene, called CHK2, appears to play a key role in the cell cycle, the process by which cells grow and divide. Both genes control checkpoints at which cells with damaged DNA should either repair themselves or stop growing, avoiding the development of cancer.

"We have found that CHK2 is a tumor suppressor gene that, when mutated, produces effects similar to those of p53 mutations. The evidence suggests it is part of the same pathway for controlling cell growth and replication," says Daniel Haber, MD, PhD, director of Cancer Risk Analysis at the MGH and leader of the study, which appears in the Dec. 24 issue of Science.

Li-Fraumeni syndrome was first described in 1969 by Frederick Li, MD, now at Dana Farber Cancer Institute, and Joseph Fraumeni, MD, of the National Cancer Institute - both of whom are co-authors of the current study. The rare condition was one of the first instances in which increased vulnerability to several types of adult cancers was clearly inherited. Identification of the tumor suppressor role of p53, along with its role in the cell cycle, directly connected a breakdown in the cell cycle with the development of cancer. It also opened up a search for other inherited cancer-related genes. Among areas in which subsequen

Contact: Susan McGreevey
Massachusetts General Hospital

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