Genetic Link Discovered Between Two Inherited Rare Diseases That Each Cause Cancer In Children

St. Jude Children's Research Hospital (ALSAC)
Friday, 17 May 2002

Interactions between the genes mutated in two different rare inherited disorders, Fanconi Anemia and Ataxia-Telangiectasia, provide new insights into tumor development and responses of tumors to therapy.

The study, led by Michael Kastan, M.D., Ph.D., and Bo Xu, M.D., Ph.D., both of the Hematology-Oncology Department at St. Jude Children's Research Hospital and Alan D'Andrea, M.D., of Dana-Farber Cancer Institute at Harvard Medical School, is featured in the May issue of Cell.

These collaborative research efforts have unveiled a genetic link between Fanconi Anemia (FA) and Ataxia Telangiectasia (AT). The insights gained help to explain the responses of both normal cells and tumor cells to radiation treatment and chemotherapy.

"We now have demonstrated that responses of cells to two different types of agents," Kastan said. "In this case, chemotherapy and radiation therapy share common components. These similarities help us better understand toxicities experienced with these therapies and could provide novel ways to enhance their effectiveness."

Chromosome breakages and cancers of the blood are clinical characteristics of both of these disorders. FA patients primarily develop myeloid leukemias and some squamous cell carcinomas and exhibit a profound sensitivity to agents that crosslink DNA. In addition to chromosomal breakage and extreme hypersensitivity to radiation. AT patients experience immunodeficiency and develop lymphoid leukemias, but they are not typically picked up through DNA testing. The findings in this study identify a specific protein that provides a linkage between the signaling pathways that help cells respond to both classes of DNA damaging agents.

"It's another step in understanding how cells respond to DNA damage which is important in both tumor development and tumor responses to therapy," Kastan said. "These studies also help us better understand the mechanisms underlying these diseases and therefore allow us to provide better treatment for our patients."

Within in the next month, St Jude will open an Ataxia Telangiectasia clinic that will treat AT patients with hematological cancers.

St. Jude Children's Research Hospital, in Memphis, Tennessee, was founded by the late entertainer Danny Thomas. The hospital is an internationally recognized biomedical research center dedicated to finding cures for catastrophic diseases of childhood. The hospital's work is supported through the funds raised by ALSAC. ALSAC covers all costs not covered by insurance for medical treatment rendered at St. Jude Children's Research Hospital. Families without insurance are never asked to pay.

For more information, or to contact St. Jude Children's Research Hospital (ALSAC), see their website at: www.stjude.org