Differential Genetic Alterations in von Hippel-Lindau Syndrome-Associated and Sporadic Pheochromocytomas1

• DOI: 10.1210/jcem.85.12.7015
• Publication Date: 2014-01-08T12:05:05Z
• Authors: Bernhard U. Bender; Markus Gutsche; Sven Gläsker; Barbara Müller; Günter Kirste; Charis Eng; Hartmut P. H. Neu...
• Keywords: Von Hippel–Lindau disease; Neurofibromatosis type 2

Pheochromocytomas arise sporadically and as a component tumor of the inherited cancer syndromes von Hippel-Lindau disease (VHL), multiple endocrine neoplasia type 2 (MEN 2), 1 neurofibromatosis. Germline mutations VHL suppressor gene (VHL) are responsible for VHL, germline RET protooncogene associated with MEN 2. The present study was conducted to examine large series 36 VHL-related pheochromocytomas somatic alterations loss heterozygosity (LOH) markers on chromosome arms 1p, 3p, 22q. For comparison, same analyses were performed in 17 sporadic pheochromocytomas. We found no intragenic within any or pheochromocytoma, pheochromocytoma demonstrated upstream hypermethylation. Of interest, we significantly different LOH frequencies at 3 loci between tumors; more than 91% 3p relatively low 1p 22q (15% 21%, respectively) argue importance dysregulation dysfunction pathogenesis almost all In contrast, frequency (24%; P ≪ 0.0001) lack compared high (71%; = 0.0003) moderate (53%) genes other especially that significant tumorigenesis suggest genetic pathways involved vs. genesis distinct.