"Pax Genes" May Hold the Key to Diagnosing and Treating a Deadly Children's Cancer

For Release on June 4, l998

Johanna Spangenberg (703) 527-7424
or Donna Krupa (703) 527-7357

"PAX GENES" MAY HOLD THE KEY TO DIAGNOSING AND TREATING A DEADLY CHILDREN'S CANCER

Pax genes are identified as a culprit in the development of tumors that occur in children and young adults

A study reveals that genetic differences can determine why one type of tumor in children under ten years of age can have a favorable prognosis, but in young adults, the same tumor can prove to be deadly. The study author, Frederic G. Barr, MD, Ph.D., from the University of Pennsylvania School of Medicine, will present this finding from his study, The Role of Chimeric Paired Box Transcription Factors in The Pathogenesis of Pediatric Rhabdomyosarcoma, at the upcoming scientific conference, "Developmental Biology and Cancer," sponsored by the General Motors Cancer Research Foundation. The 20th Annual Conference of the General Motors Cancer Research Foundation, is being held June 9-10, 1998, at the Jack Masur Auditorium, National Institutes of Health, Bethesda, MD.

Background: Alveolar rhabdomyosarcoma (ARMS) is a soft tissue tumor that is derived from striated (skeletal) muscle, and is most commonly found in pediatric patients. The disease often occurs in the extremities and trunk of adolescents and young adults; prognosis for the patient is often unfavorable. Cytogenetic studies have identified nonrandom, chromosomal translocations (change of two segments between dissimilar chromosomes). Specifically, translocations involving chromosomes 2 and 13 were detected in 70% of published ARMS cases, and translocations with 1 and 13 appeared in a variant manner. Both these translocations are specific markers for ARMS.

Conclusion Using a physical gene-mapping approach, Dr. Barr's objective was to discover the molecular basis for the 2;13 and 1;13 chromosomal translocations that occur in ARMS. He found that within ARMS, the translocations 2;13 and 1;13 juxtapose Pax genes PAX3 or PAX7, with another gene FKHR, to produce PAX3-FKHR and PAX7-FKHR.

Essentially, tumor cells from different ARMS tumors appear identical under a microscope. However, genetic mapping of the tumor cells can specifically identify whether PAX3-FKHR or PAX7-FKHR is present, and provide clues on the clinical impact of the respective tumors.

The Barr study suggests that future studies continue to establish how the Pax gene fusions contribute to the tumor development process and explain the biological differences between the two fusion types. It is expected that knowledge of this area will dictate the directions of new strategies to create an effective intervention designed to halt tumor growth.

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(Editor's Note: A newsroom will be open during the conference. Contact Johanna Spangenberg (703) 527-7424 or JMSDC @aol.com for additional information or to arrange an interview with Dr. Barr regarding his research.)