SPORADIC PHEOCHROMOCYTOMAS ARE RARELY ASSOCIATED WITH GERMLINE MUTATIONS IN THE VON-HIPPEL-LINDAU AND RET GENES

OBJECTIVE von Hippel-Lindau (VHL) disease and multiple endocrine neopl asia type 2 (MENS) are autosomal dominant cancer syndromes. In both co nditions, phaeochromocytoma is a prominent feature. it has recently be en suggested that phaeochromocytoma can be the presenting and sole cli nical manifestation of these multi-organ syndromes. The aim of this st udy was to ascertain the incidence of VHL and MEN2 among patients with sporadic phaeochromocytoma by mutational analysis, PATIENTS Twenty-se ven unrelated patients with biochemically and/or anatomically proven s poradic phaeochromocytoma were evaluated, DESIGN AND MEASUREMENTS Cons titutional DNA obtained from the patients was analysed by single stran ded conformational analysis (SSCP) for mutations within the VHL gene c oding sequence and by denaturing gradient gel electrophoresis (DGGE) f or predominant mutations in exons 10, 11 and 16 of the RET proto-oncog ene, The incidence of patients positive for either VHL or RET germline mutations was assessed. RESULTS Twenty-six of 27 patients had normal SSCP patterns in all three VHL gene exon segments and only one patient , with an atypical clinical presentation, had an aberrant pattern in e xon 3 which upon DNA sequencing was shown to harbor a G to A transvers ion mutation at nucleotide 695., All patients had normal RET exon 10, 11 and 16 DGGE migration patterns. CONCLUSION Most, if not all, patien ts with typical unilateral sporadic phaeochromocytoma do not have von Hippel-Lindau disease or MENS. Thus, clinical and/or molecular investi gation for von Hippel-Lindau disease and MEN2 in this patient populati on does not appear to be indicated.