SPORADIC PHEOCHROMOCYTOMAS ARE RARELY ASSOCIATED WITH GERMLINE MUTATIONS IN THE VHL TUMOR-SUPPRESSOR GENE OR THE RET PROTOONCOGENE

Pheochromocytoma is a tumor that may occur sporadically or may be a ma nifestation of a hereditary disease, such as von Hippel-Lindau disease (VHL) and multiple endocrine neoplasia (MEN) type 2. As patients with VHL or MEN type 2 are at risk to develop multiple tumors, they must b e distinguished from sporadic cases. We determined the incidence of VH L and MEN type 2 among 62 German patients diagnosed with pheochromocyt oma without a history of a hereditary disease. Germline analyses of th e vhl gene and exons 10, 11, and 13 of the ret protooncogene were perf ormed by PCR, single strand conformation polymorphism, enzyme digestio n, or sequencing. Two patients (3%) showed vhl mutations (95% confiden ce interval, 1-11%). One patient showed loss of the MspI restriction s ite at nucleotides 712/713. Another patient had a C/T change at an int ronic site that was also detected in 2 of his offspring. No mutations were detected in the ret protooncogene (97.5% confidence interval, 0-6 %). In Germany, most sporadic pheochromocytomas are not due to VHL or MEN type 2. Therefore, clinical work-up in patients with pheochromocyt oma without signs of hereditary disease is not recommended. However, b ecause the costs of genetic screening are relatively low, and each ind ex case allows optimal care for family members, molecular testing migh t be cost-effective.