GENE TESTING CAN GUIDE CARE OF PEOPLE WITH RARE TUMORS
COLUMBUS, Ohio – People with rare tumors known as pheochromocytomas and paragangliomas, irregardless of family history, need to seek genetic counseling and testing for mutations in one of at least four genes to see if they carry an inherited predisposition for the diseases. If they do, then close relatives should also consider genetic testing to look for the same mutation and to guide preventive care in those who do.
Those recommendations come from a study led by researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute.
The study looked at the syndromes caused by the two most commonly mutated genes and revealed clinical symptom differences that should help determine which gene tests should be given first, thereby reducing the number of needless tests. It also will help guide preventive care in people born with the mutations but who have not yet showed signs of disease.
The findings are published in the Aug. 25 issue of the Journal of the American Medical Association.
“This study provides preliminary guidance for genetic counseling and medical surveillance in people with mutations in these two genes,” says study leader Charis Eng, MD, PhD, the Dorothy E. Klotz Chair of Cancer Research and director of the clinical cancer genetics program.
The research examined genes for succinate dehydrogenase subunit B (SDHB) and for succinate dehydrogenase subunit D (SDHD).
Mutations in the SDHB gene cause paraganglioma syndromes type 4 (PGL-4), while mutations in the SDHD gene cause paraganglioma syndromes type 1 (PGL-1). Both syndromes give rise to pheochromocytomas and paragangliomas, tumors that are usually benign.
Pheochromocytomas are hormone-producing tumors that occur in the adrenal glands, abdomen and chest. Paragangliomas are related tumors that develop mainly in the head and neck. About one person in 200,000 to 300,000 develops pheochromocytomas or paragangliomas.
The study sought to determine the characteristics, or clinical features, of the syndromes that develop in people born with so-called “germline mutations” in the SDHB and SDHD genes. Germline mutations are inherited from a parent and are present in all cells of the body.
Using population-based registries in Germany and another in Poland, the researchers identified 334 people with pheochromocytomas and 83 people with head and neck paragangliomas. Genetic testing showed that 25 of the people with pheochromocytomas carried germline mutations in the SDHB gene, and 24 of those with paragangliomas had germline mutations in the SDHD gene.
The researchers then offered genetic testing to immediate family members (i.e., mother, father, siblings) of these individuals. Of 161 eligible relatives, 103 accepted testing. In all, 53 people had SDHB germline mutations, and 47 people had SDHD germline mutations. No one had mutations in both genes.
Each person was examined for the presence of tumors using both magnetic resonance imaging (MRI) and computerized tomography (CT) scanning; and hormone levels were measured in urine samples. The results were compared for similarities and differences in the tumors caused by each of the two mutated genes.
The findings showed that the average age of diagnosis in both cases was 29 years. (Earlier work led by Eng, published in 2002 in the New England Journal of Medicine, showed that tumors can also develop in patients up to age 70 or later.) They also showed the following:
“Mutations in the SDHB gene seem to cause disease less often, but when they do, it can be more serious,” says Eng, a recipient of the Doris Duke Distinguished Clinical Scientist Award.
If confirmed, the findings suggest that all individuals diagnosed with head and neck paragangliomas should receive gene counseling and testing for SDHD mutations first, while those with pheochromocytomas in the abdomen or chest, or with cancerous tumors, should be tested first for SDHB mutations.
The research also suggest that preventive care for persons with germline mutations in the SDHB gene and no signs of disease (e.g., a first-degree relative of someone with pheochromocytoma) should include annual testing (e.g., by MRI) to identify tumors early.
Individuals with germline mutations in the SDHD gene should consider
similar testing for head and neck paragangliomas, Eng says.
Contact: Darrell E. Ward, Medical Center Communications, 614-293-3737,