Loss of heterozygosity on the short arm of chromosome 3 in sporadic, von hippel‐lindau disease‐associated, and familial pheochromocytoma

Abstract

Pheochromocytomas occur sporadically and are associated with several dominantly inherited cancer syndromes, including von Hippel-Lindau (VHL) disease. We examined 14 pheochromocytomas (four from VHL patients, nine from sporadic patients, and one from a patient with familial pheochromocytoma) for loss of heterozygosity on chromosome arm 3p by using the polymerase chain reaction and restriction fragment length polymorphisms at eight loci. Loss of heterozygosity was detected in 8 of 14 pheochromocytomas examined: in three of the four VHL-associated tumors, in four of the nine sporadic tumors, and in the familial pheochromocytoma-associated tumor. Deletion of the inherited wild-type VHL allele was demonstrated in both informative VHL-associated pheochromocytomas, demonstrating involvement of VHL in pheochromocytoma development. However, because VHL mutations have not been detected in sporadic pheochromocytomas, VHL and/or another chromosome arm 3p gene may be involved in the etiology of these tumors.