Pheochromocytoma in rats with multiple endocrine neoplasia (MENX) shares gene expression patterns with human pheochromocytoma

MENX is a rat multiple endocrine neoplasia syndrome caused by a homozygous mutation of the Cdkn1b gene, encoding p27Kip1. Affected rats develop adrenomedullary hyperplasia which progresses to pheochromocytoma with time (incidence 100%), and to extra-adrenal pheochromocytoma (paraganglioma) (68%). We here report that hyperplasia and tumor have similar gene expression profiles, suggesting an early determination of the tumorigenic signature. Overexpressed genes in rat adrenal lesions are especially enriched in development/differentiation-associated genes. We performed gene expression microarray analysis of 8 adrenal hyperplasias and 4 pheochromocytomas, each compared with adrenomedullary tissue from wild-type, age-matched littermates.