Families and Scientists Gather to Discuss Research and Treatment for Li-Fraumeni Syndrome
Earlier this month, about 200 people gathered at the NIH Natcher Conference Center for an international workshop to review the current status of research on a rare, inherited disorder known as Li-Fraumeni syndrome (LFS). In attendance were researchers, clinicians, genetic counselors, and members of approximately 40 families that are affected by the disease. Drs. Sharon Savage and Phuong Mai, of the Clinical Genetics Branch in NCI’s Division of Cancer Epidemiology and Genetics (DCEG), organized the workshop.
“I’m only 40 years old,” a woman in the audience shared after listening to a panel of patients speak about LFS. “I’ve lost a child to cancer, and I’ve had cancer six times. I [knew of] no one else who has this [syndrome].” Moved to tears, she went on to describe the experience of dealing with the fear of cancer every day and knowing that her surviving daughter could be diagnosed with cancer at any time. “I have cancer right now,” she said, “and it’s just so overwhelming to hear someone else’s story and know that I’m not alone anymore.”
—LFS survivor in audience
Li-Fraumeni syndrome was first described in a 1969 publication in the Annals of Internal Medicine by Dr. Joseph F. Fraumeni, Jr., the director of DCEG, and his colleague Dr. Frederick P. Li. They described four families in which several members developed a wide variety of cancers as children or young adults. Many of the patients had multiple primary tumors, most notably breast cancer, soft tissue and bone sarcomas, brain tumors, adrenocortical neoplasms, and acute leukemia. Subsequent studies identified additional families that met the classic criteria for LFS. Other families had similar but less pronounced aggregations of cancer and were classified as Li-Fraumeni-like (LFL).
Families with LFS have been found to have inherited mutations in the TP53 gene, a tumor suppressor gene involved in numerous cellular processes, including DNA repair and apoptosis. But only about 70 percent of families with classic LFS and 40 percent of LFL families carry these mutations, so the genetic determinants in other patients remain unknown. “We need a coordinated global effort if we are to succeed against this rare disorder,” Dr. Fraumeni said at the start of the meeting. “This is a very exciting time in cancer genomics, and research on this syndrome can take full advantage of the opportunities and technologies these advances provide.”
Reflecting on Success and Teamwork
Dr. Louise Strong from the University of Texas M. D. Anderson Cancer Center discussed the history of research on LFS, including the early work of scientists who persisted in tracking families that showed characteristics of the syndrome while collecting biospecimens for future molecular studies. One of the many positive outcomes of the workshop was the establishment of a new LFS clinical research consortium to develop protocols that require pooling of data and resources. This international collaboration will focus on improvements in screening, treatment, and prevention, as well as interdisciplinary research into the mechanisms underpinning multiple-cancer syndromes such as LFS.
During a panel that included patients and their families, Oliver Wyss told the audience, “We have to look at this workshop as a gathering of one big family, working against this devastating disease to find a cure.” Wyss was diagnosed with severe aplastic anemia at the age of 22 after coming to the United States to play professional soccer. He recovered from the disease and has been healthy ever since, but, when his son was diagnosed at the age of 10 months with choroid plexus carcinoma, an extremely rare tumor, the family was tested and learned that they all carry a germline TP53 mutation that causes LFS. His son died at age 3 after numerous rounds of surgery, chemotherapy, and radiation treatments. In addition, his daughter was recently diagnosed with adrenocortical carcinoma.
“I believe I speak for all of the families here [when I say] there isn’t enough going on. We can’t just be satisfied by screening for cancer,” he said. “We have to find true cures for these genetic disorders. As families, we’re willing to do more, to give back.”
Reflecting on the successful workshop and development of a consortium, Dr. Savage said, “through our ongoing study of LFS families at NCI and through our collaborative approach we hope to not only help those with the disorder but also provide clues for future research into the genetic underpinnings of nonfamilial tumors.”
Focusing on the Future
During a plenary session on the clinical aspects of LFS, Dr. Maria Isabel Waddington Achatz of São Paolo, Brazil, described studies of high-risk families that feature adrenocortical tumors in children. She estimated that, in the southeastern portion of Brazil, one in every 300 people is the carrier of a distinctive founder mutation in TP53.
Other plenary sessions at the meeting addressed concerns related to genetic counseling for LFS and LFL patients, the psychosocial aspects of having the disorder, and the molecular biology of TP53. Participants met in smaller groups at the end of the workshop to discuss how they could work together to hasten progress in clinical and interdisciplinary research and how to establish a family support network for those who deal with this disorder every day.
“I was truly delighted to participate in this historic event,” said Dr. Fraumeni. “This is an exciting time for research on LFS. The new consortium of investigators that pools expertise and resources, combined with the development of an advocacy organization to support families, holds great promise for this important field of study.”
An archived video of the full meeting is available through the NIH Videocast Web site.