Genetic specialists at Dana-Farber/Children's Hospital Cancer Center (DF/CHCC) are recommending that children being treated for sarcoma should be offered genetic counseling for Li-Fraumeni syndrome, a rare condition that greatly raises a person's risk of developing additional cancers.
The recommendation was made in light of research that has identified a link between sarcoma, a tumor of the bone or soft tissue like muscle and fat, and Li-Fraumeni syndrome.
"Identification of an inherited gene alteration can sometimes help guide current treatment decisions and may also help with early detection and cancer prevention in the future," says Carly F. Grant, MS, CGC, a genetic counselor of the Pediatric Cancer
Risk Program at DF/CHCC, one of the first programs in the country that provides multidisciplinary consultative care to patients and their families whose condition or family history suggests an increased risk of cancer.
Li-Fraumeni syndrome was first described in 1969 by Dana-Farber physician-scientist Frederick Li, MD, and his mentor, Joseph F. Fraumeni Jr., MD, of the National Cancer Institute. In 1990, researchers discovered that the increased risk of cancer associated
with the syndrome is caused by inherited changes in the tp53 gene – a finding that made genetic testing for Li-Fraumeni syndrome possible.
Cancers typically diagnosed in patients with Li-Fraumeni syndrome include breast cancer, sarcomas (including soft tissue and osteosarcomas, but not Ewing sarcoma), brain tumors, acute leukemia, and adrenal cortical carcinoma. Recently, the list has been
expanded to include colon cancer and stomach cancer, following discoveries by Dana-Farber researchers Sapna Syngal, MD, MPH, Serena Masciari, MD, and Judy Garber, MD, MPH, director of Dana-Farber's Cancer Genetics and Prevention Program. Fewer than 1,000 families with Li-Fraumeni syndrome have been identified
worldwide, but research has shown that childhood sarcomas are one of the characteristic cancers associated with Li-Fraumeni syndrome.
Fewer than 10 percent of children with sarcomas harbor a tp53 mutation, and while most children inherit the tp53 mutation from a parent, it's also possible for someone to be born with a new mutation. Individuals who carry a tp53 mutation have a 50 percent chance of passing it on to each of his or her children. There are benefits and drawbacks to genetic testing for the tp53 mutation; genetic counselors can provide families with the information they need to make informed
decisions about whether or not to undergo genetic testing, as for all aspects of their child's care.
For example, because people with Li-Fraumeni syndrome are especially sensitive to carcinogenic effects of radiation, which has been linked to the development of future cancers in some patients, knowing whether or not a child carries a tp53 mutation
may influence how the care team weighs the benefits and risks of radiation treatment.
In addition, because the tp53 mutation is typically inherited, there may be other family members at risk who would also have the option of being tested. Children who test positive can then be more carefully monitored by their physicians, while
adults may be advised to be screened more frequently for certain cancers, and to start screening at an earlier age.
The information may also be helpful for adults with Li-Fraumeni syndrome who are already being treated for cancer. Garber is pursuing leads suggesting that breast cancers in Li-Fraumeni syndrome patients could be treated by the targeted drug Herceptin.
While there have been few effective cancer screening methods specifically for people with Li-Fraumeni syndrome, new screening methods are emerging.
In an encouraging study published in 2008 by Garber, Masciari, Syngal, Lisa Diller, MD, and other Dana-Farber physician-scientists, PET-CT scans detected three cancers in 15 Li-Fraumeni patients who were not
experiencing any symptoms.
In the coming months, Diller and a team of Dana-Farber scientists will launch a new study testing the effectiveness of rapid full-body MRI scans for children and adults with Li-Fraumeni syndrome. The goal is to learn how to find cancers early and treat
them effectively in people with Li-Fraumeni syndrome.
Diller and Allison O'Neill, MD, and other Dana-Farber/Children's Hospital Cancer Center scientists are also working to launch a national study on other screening options.
"Genetic testing may provide important information about cancer risks and medical management options that can be invaluable to a patient and their team of oncologists and specialists," Grant says.